首页 > 最新文献

American journal of physiology. Cell physiology最新文献

英文 中文
Alterations in the transcriptome and microRNAs of adipose-derived mesenchymal stem cells from different sites in rats during aging. 大鼠不同部位脂肪间充质干细胞转录组和 microRNA 在衰老过程中的变化。
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1152/ajpcell.00044.2024
Zhenyang Su, Tianhua Xu, Jin-Yu Sun, Wei Sun, Xiangqing Kong

Aging is an intricate and gradual process characterized by tissue and cellular dysfunction. Adipose-derived mesenchymal stem cells (ADMSCs) experience a functional decline as part of systemic aging. However, the alterations in ADMSCs across various anatomical sites throughout an individual's lifespan remain unclear. To shed light on these changes, we collected white adipose tissue and brown adipose tissue samples from the epididymis, perirenal, inguinal, and scapular regions of young, adult, and aged rats and subsequently isolated ADMSCs for RNA sequencing. As aging progressed, we observed a reduction in the number of ADMSCs at all anatomical sites. Marker genes of ADMSCs from different sites were identified. Aging triggered notable activation of inflammatory and immune responses while diminishing the ADMSC differentiation capacity and ability to maintain normal tissue morphology. Furthermore, miR-195-5p and miR-497-3p, which promoted cell senescence and apoptosis while inhibiting proliferation and differentiation, were positively correlated with aging. These findings increase our understanding of ADMSC senescence and underscore the unique physiological changes and functions of ADMSCs across different anatomical sites during aging.

衰老是一个错综复杂的渐进过程,其特点是组织和细胞功能失调。脂肪间充质干细胞(ADMSCs)会随着全身衰老而出现功能衰退。然而,ADMSCs在人的一生中不同解剖部位的变化仍不清楚。为了揭示这些变化,我们从幼鼠、成年鼠和老龄鼠的附睾、肾周、腹股沟和肩胛区采集了白色脂肪组织和棕色脂肪组织样本,随后分离出 ADMSCs 进行 RNA 测序。随着年龄的增长,我们观察到所有解剖部位的 ADMSC 数量都在减少。我们确定了不同部位 ADMSCs 的标记基因。衰老显著激活了炎症和免疫反应,同时降低了 ADMSC 的分化能力和维持正常组织形态的能力。此外,促进细胞衰老和凋亡同时抑制增殖和分化的 miR-195-5p 和 miR-497-3p 与衰老呈正相关。这些发现增加了我们对 ADMSC 衰老的了解,并强调了 ADMSC 在衰老过程中不同解剖部位的独特生理变化和功能。
{"title":"Alterations in the transcriptome and microRNAs of adipose-derived mesenchymal stem cells from different sites in rats during aging.","authors":"Zhenyang Su, Tianhua Xu, Jin-Yu Sun, Wei Sun, Xiangqing Kong","doi":"10.1152/ajpcell.00044.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00044.2024","url":null,"abstract":"<p><p>Aging is an intricate and gradual process characterized by tissue and cellular dysfunction. Adipose-derived mesenchymal stem cells (ADMSCs) experience a functional decline as part of systemic aging. However, the alterations in ADMSCs across various anatomical sites throughout an individual's lifespan remain unclear. To shed light on these changes, we collected white adipose tissue and brown adipose tissue samples from the epididymis, perirenal, inguinal, and scapular regions of young, adult, and aged rats and subsequently isolated ADMSCs for RNA sequencing. As aging progressed, we observed a reduction in the number of ADMSCs at all anatomical sites. Marker genes of ADMSCs from different sites were identified. Aging triggered notable activation of inflammatory and immune responses while diminishing the ADMSC differentiation capacity and ability to maintain normal tissue morphology. Furthermore, miR-195-5p and miR-497-3p, which promoted cell senescence and apoptosis while inhibiting proliferation and differentiation, were positively correlated with aging. These findings increase our understanding of ADMSC senescence and underscore the unique physiological changes and functions of ADMSCs across different anatomical sites during aging.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune system activation and cognitive impairment in arterial hypertension. 动脉高血压的免疫系统激活和认知障碍。
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1152/ajpcell.00219.2024
Stefanie Schreiber, Philipp Arndt, Lorena Morton, Alejandra P Garza, Patrick Müller, Katja Neumann, Hendrik Mattern, Marc Dörner, Jose Bernal, Stefan Vielhaber, Sven G Meuth, Ildiko R Dunay, Alexander Dityatev, Solveig Henneicke

Chronic arterial hypertension disrupts the integrity of the cerebral microvasculature, doubling the risk of age-related dementia. Despite sufficient antihypertensive therapy, in still a significant proportion of individuals blood pressure lowering alone does not preserve cognitive health. Accumulating evidence highlights the role of inflammatory mechanisms in the pathogenesis of hypertension. In this review, we introduce a temporal framework to explore how early immune system activation and interactions at neurovascular-immune interfaces pave the way to cognitive impairment. The overall paradigm suggests that pro-hypertensive stimuli induce mechanical stress and systemic inflammatory responses that shift peripheral and meningeal immune effector mechanisms towards a pro-inflammatory state. Neurovascular-immune interfaces in the brain include a dysfunctional blood-brain barrier, crossed by peripheral immune cells; the perivascular space, in which macrophages respond to cerebrospinal fluid- and blood-derived immune regulators; and the meningeal immune reservoir, particularly T cells. Immune responses at these interfaces bridge peripheral and neurovascular unit inflammation, directly contributing to impaired brain perfusion, clearance of toxic metabolites and synaptic function. We propose that deep immunophenotyping in biofluids together with advanced neuroimaging could aid in the translational determination of sequential immune and brain endotypes specific to arterial hypertension. This could close knowledge gaps on how and when immune system activation transits into neurovascular dysfunction and cognitive impairment. In the future, targeting specific immune mechanisms could prevent and halt hypertension disease progression before clinical symptoms arise, addressing the need for new interventions against one of the leading threats to cognitive health.

慢性动脉高血压会破坏脑微血管的完整性,使老年痴呆症的风险增加一倍。尽管进行了充分的降压治疗,但仍有相当一部分人单靠降压并不能保持认知健康。越来越多的证据凸显了炎症机制在高血压发病机制中的作用。在这篇综述中,我们介绍了一个时间框架,以探讨早期免疫系统激活和神经血管-免疫界面的相互作用如何为认知障碍铺平道路。总体范式表明,促高血压刺激会诱发机械应激和全身炎症反应,从而使外周和脑膜免疫效应机制转向促炎症状态。大脑中的神经血管-免疫界面包括功能失调的血脑屏障,由外周免疫细胞穿过;血管周围空间,其中巨噬细胞对脑脊液和血液衍生的免疫调节剂做出反应;以及脑膜免疫库,尤其是 T 细胞。这些界面上的免疫反应是外周和神经血管单元炎症的桥梁,直接导致脑灌注、有毒代谢物清除和突触功能受损。我们建议,生物流体中的深度免疫分型与先进的神经影像学相结合,可帮助转化确定动脉高血压特有的连续免疫和大脑内型。这将填补有关免疫系统激活如何以及何时转变为神经血管功能障碍和认知障碍的知识空白。未来,针对特定的免疫机制可以在临床症状出现之前预防和阻止高血压疾病的发展,从而满足对认知健康的主要威胁之一的新干预措施的需求。
{"title":"Immune system activation and cognitive impairment in arterial hypertension.","authors":"Stefanie Schreiber, Philipp Arndt, Lorena Morton, Alejandra P Garza, Patrick Müller, Katja Neumann, Hendrik Mattern, Marc Dörner, Jose Bernal, Stefan Vielhaber, Sven G Meuth, Ildiko R Dunay, Alexander Dityatev, Solveig Henneicke","doi":"10.1152/ajpcell.00219.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00219.2024","url":null,"abstract":"<p><p>Chronic arterial hypertension disrupts the integrity of the cerebral microvasculature, doubling the risk of age-related dementia. Despite sufficient antihypertensive therapy, in still a significant proportion of individuals blood pressure lowering alone does not preserve cognitive health. Accumulating evidence highlights the role of inflammatory mechanisms in the pathogenesis of hypertension. In this review, we introduce a temporal framework to explore how early immune system activation and interactions at neurovascular-immune interfaces pave the way to cognitive impairment. The overall paradigm suggests that pro-hypertensive stimuli induce mechanical stress and systemic inflammatory responses that shift peripheral and meningeal immune effector mechanisms towards a pro-inflammatory state. Neurovascular-immune interfaces in the brain include a dysfunctional blood-brain barrier, crossed by peripheral immune cells; the perivascular space, in which macrophages respond to cerebrospinal fluid- and blood-derived immune regulators; and the meningeal immune reservoir, particularly T cells. Immune responses at these interfaces bridge peripheral and neurovascular unit inflammation, directly contributing to impaired brain perfusion, clearance of toxic metabolites and synaptic function. We propose that deep immunophenotyping in biofluids together with advanced neuroimaging could aid in the translational determination of sequential immune and brain endotypes specific to arterial hypertension. This could close knowledge gaps on how and when immune system activation transits into neurovascular dysfunction and cognitive impairment. In the future, targeting specific immune mechanisms could prevent and halt hypertension disease progression before clinical symptoms arise, addressing the need for new interventions against one of the leading threats to cognitive health.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ciliopathy Organoid Models - a Comprehensive Review. 纤毛虫病类器官模型--全面回顾。
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1152/ajpcell.00343.2024
Matylda Zofia Kuzinska, Sally Yuan-Yin Lin, Verena Klämbt, Philip Bufler, Milad Rezvani

Cilia are membrane-bound organelles found on the surface of most mammalian cell types and play numerous roles in human physiology and development, including osmo- and mechanosensation, as well as signal transduction. Ciliopathies are a large group of - usually rare - genetic disorders resulting from abnormal ciliary structure or ciliary dysfunction that have a high collective prevalence. Autosomal dominant or recessive polycystic kidney disease (ADPKD/ARPKD), Bardet-Biedl-Syndrome and primary ciliary dyskinesia (PCD) are the most frequent etiologies. Rodent and zebrafish models have improved the understanding of ciliopathy pathophysiology. Yet, the limitations of these genetically modified animal strains include the inability to fully replicate the phenotypic heterogeneity found in humans, including variable multi-organ involvement. Organoids, self-assembled 3D-cell-based models derived from human induced pluripotent stem cells (iPSCs) or primary tissues, can recapitulate certain aspects of the development, architecture, and function of the target organ in the dish. The potential of organoids to model patient-specific genotype-phenotype correlations has increased their popularity in ciliopathy research and led to the first preclinical organoid-based ciliopathy drug screens. This review comprehensively summarizes and evaluates current ciliopathy organoid models, focusing on kidney, airway, liver, and retinal organoids, as well as the specific methodologies used for their cultivation and for interrogating ciliary dysfunction.

纤毛是大多数哺乳动物细胞表面的膜结合细胞器,在人体生理和发育过程中扮演着多种角色,包括渗透和机械感觉以及信号转导。纤毛疾病是由纤毛结构异常或纤毛功能障碍导致的一大类遗传性疾病,通常比较罕见,集体发病率很高。常染色体显性或隐性多囊肾病(ADPKD/ARPKD)、巴尔德-比德尔综合征(Bardet-Biedl-Syndrome)和原发性纤毛运动障碍(PCD)是最常见的病因。啮齿动物和斑马鱼模型增进了人们对纤毛病病理生理学的了解。然而,这些转基因动物品系的局限性包括无法完全复制人类的表型异质性,包括可变的多器官受累。器官组织是一种基于三维细胞的自组装模型,由人类诱导多能干细胞(iPSCs)或原始组织衍生而来,可在培养皿中再现目标器官的某些发育、结构和功能。有机体在模拟患者特异性基因型-表型相关性方面的潜力使其在纤毛虫病研究中越来越受欢迎,并促成了首次基于临床前有机体的纤毛虫病药物筛选。本综述全面总结和评估了当前的纤毛器病变类器官模型,重点关注肾脏、气道、肝脏和视网膜类器官,以及用于培养和检测纤毛功能障碍的具体方法。
{"title":"Ciliopathy Organoid Models - a Comprehensive Review.","authors":"Matylda Zofia Kuzinska, Sally Yuan-Yin Lin, Verena Klämbt, Philip Bufler, Milad Rezvani","doi":"10.1152/ajpcell.00343.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00343.2024","url":null,"abstract":"<p><p>Cilia are membrane-bound organelles found on the surface of most mammalian cell types and play numerous roles in human physiology and development, including osmo- and mechanosensation, as well as signal transduction. Ciliopathies are a large group of - usually rare - genetic disorders resulting from abnormal ciliary structure or ciliary dysfunction that have a high collective prevalence. Autosomal dominant or recessive polycystic kidney disease (ADPKD/ARPKD), Bardet-Biedl-Syndrome and primary ciliary dyskinesia (PCD) are the most frequent etiologies. Rodent and zebrafish models have improved the understanding of ciliopathy pathophysiology. Yet, the limitations of these genetically modified animal strains include the inability to fully replicate the phenotypic heterogeneity found in humans, including variable multi-organ involvement. Organoids, self-assembled 3D-cell-based models derived from human induced pluripotent stem cells (iPSCs) or primary tissues, can recapitulate certain aspects of the development, architecture, and function of the target organ <i>in the dish</i>. The potential of organoids to model patient-specific genotype-phenotype correlations has increased their popularity in ciliopathy research and led to the first preclinical organoid-based ciliopathy drug screens. This review comprehensively summarizes and evaluates current ciliopathy organoid models, focusing on kidney, airway, liver, and retinal organoids, as well as the specific methodologies used for their cultivation and for interrogating ciliary dysfunction.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The HIF2α-dependent Upregulation of SETDB1 Facilitates Hypoxia-induced Functional and Phenotypical Changes of Pulmonary Microvascular Endothelial Cells. HIF2α依赖的SETDB1上调促进了缺氧诱导的肺微血管内皮细胞功能和表型变化
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1152/ajpcell.00732.2023
Yin Zhou, Kai Yang, Zizhou Zhang, Feng Wei, Lishi Chen, Dongling Luo, Ziyang Yang, Kaixun Zhao, Nanshan Xie, Wenrui Li, Shuxin Liang, Mingmei Xiong, Haiyang Tang, Jian Wang, Caojin Zhang

Background: Emerging studies have reported the vital role of histone modification in the dysfunction of pulmonary vascular endothelial cells, which acts as the key reason to drive the hypoxia-induced pulmonary vascular remodeling and pulmonary hypertension (PH). This study aims to investigate the role of a histone 3 lysine 9 (H3K9) methyltransferase, SET domain bifurcated 1 (SETDB1), in hypoxia-induced functional and phenotypical changes of pulmonary vascular endothelial cells. Methods: Primarily cultured rat pulmonary microvascular endothelial cells (PMVECs) were used as cell model. Specific knockdown and overexpression strategies were used to systematically determine the molecular regulation and function of SETDB1 in PMVECs. Results: SETDB1 is highly expressed and significantly upregulated in the pulmonary vascular endothelium of lung tissue isolated from SU5416/hypoxia-induced PH (SuHx-PH) rats, and also in pulmonary arterial endothelial cells (PAECs) from idiopathic pulmonary arterial hypertension (IPAH) patients, comparing to their respective controls. In primarily cultured rat PMVECs, treatment of hypoxia or CoCl2 induces significant upregulation of HIF2α, SETDB1 and H3K9me3. Specific knockdown and overexpression strategies indicate the hypoxia- or CoCl2-induced upregulation of SETDB1 is mediated through a HIF2α-dependent mechanism. Knockdown of SETDB1 significantly inhibits the hypoxia- or CoCl2-induced apoptosis, senescence and endothelial to mesenchymal transition (EndoMT) in rat PMVECs. Moreover, treatment of the specific inhibitor of histone methyltransferase, Chaetocin, effectively attenuates the disease pathogenesis of SuHx-PH in rat. Conclusions: Our results suggest that the HIF2α-dependent upregulation of SETDB1 facilitates hypoxia-induced functional and phenotypical changes of PMVECs, potentially contributing to the hypoxia-induced pulmonary vascular remodeling and PH.

背景:新近的研究报道了组蛋白修饰在肺血管内皮细胞功能障碍中的重要作用,而肺血管内皮细胞功能障碍是驱动缺氧诱导的肺血管重塑和肺动脉高压(PH)的关键原因。本研究旨在探讨组蛋白 3 赖氨酸 9(H3K9)甲基转移酶 SET domain bifurcated 1(SETDB1)在缺氧诱导的肺血管内皮细胞功能和表型变化中的作用。研究方法以原始培养的大鼠肺微血管内皮细胞(PMVECs)为细胞模型。采用特定的基因敲除和过表达策略,系统测定 SETDB1 在 PMVECs 中的分子调控和功能。结果发现与各自的对照组相比,SETDB1在分离自SU5416/缺氧诱导的PH(SuHx-PH)大鼠肺组织的肺血管内皮细胞以及特发性肺动脉高压(IPAH)患者的肺动脉内皮细胞(PAECs)中高表达并显著上调。在主要培养的大鼠 PMVECs 中,缺氧或 CoCl2 处理会诱导 HIF2α、SETDB1 和 H3K9me3 的显著上调。特定的敲除和过表达策略表明,缺氧或CoCl2诱导的SETDB1上调是通过HIF2α依赖机制介导的。敲除 SETDB1 能显著抑制缺氧或 CoCl2- 诱导的大鼠 PMVECs 细胞凋亡、衰老和内皮细胞向间质转化(EndoMT)。此外,组蛋白甲基转移酶的特异性抑制剂Chaetocin能有效减轻大鼠SuHx-PH的发病机制。结论我们的研究结果表明,HIF2α依赖的SETDB1上调促进了缺氧诱导的PMVECs的功能和表型变化,可能是缺氧诱导的肺血管重塑和PH的原因之一。
{"title":"The HIF2α-dependent Upregulation of SETDB1 Facilitates Hypoxia-induced Functional and Phenotypical Changes of Pulmonary Microvascular Endothelial Cells.","authors":"Yin Zhou, Kai Yang, Zizhou Zhang, Feng Wei, Lishi Chen, Dongling Luo, Ziyang Yang, Kaixun Zhao, Nanshan Xie, Wenrui Li, Shuxin Liang, Mingmei Xiong, Haiyang Tang, Jian Wang, Caojin Zhang","doi":"10.1152/ajpcell.00732.2023","DOIUrl":"https://doi.org/10.1152/ajpcell.00732.2023","url":null,"abstract":"<p><p><i>Background:</i> Emerging studies have reported the vital role of histone modification in the dysfunction of pulmonary vascular endothelial cells, which acts as the key reason to drive the hypoxia-induced pulmonary vascular remodeling and pulmonary hypertension (PH). This study aims to investigate the role of a histone 3 lysine 9 (H3K9) methyltransferase, SET domain bifurcated 1 (SETDB1), in hypoxia-induced functional and phenotypical changes of pulmonary vascular endothelial cells. <i>Methods:</i> Primarily cultured rat pulmonary microvascular endothelial cells (PMVECs) were used as cell model. Specific knockdown and overexpression strategies were used to systematically determine the molecular regulation and function of SETDB1 in PMVECs. <i>Results:</i> SETDB1 is highly expressed and significantly upregulated in the pulmonary vascular endothelium of lung tissue isolated from SU5416/hypoxia-induced PH (SuHx-PH) rats, and also in pulmonary arterial endothelial cells (PAECs) from idiopathic pulmonary arterial hypertension (IPAH) patients, comparing to their respective controls. In primarily cultured rat PMVECs, treatment of hypoxia or CoCl<sub>2</sub> induces significant upregulation of HIF2α, SETDB1 and H3K9me3. Specific knockdown and overexpression strategies indicate the hypoxia- or CoCl<sub>2</sub>-induced upregulation of SETDB1 is mediated through a HIF2α-dependent mechanism. Knockdown of SETDB1 significantly inhibits the hypoxia- or CoCl<sub>2</sub>-induced apoptosis, senescence and endothelial to mesenchymal transition (EndoMT) in rat PMVECs. Moreover, treatment of the specific inhibitor of histone methyltransferase, Chaetocin, effectively attenuates the disease pathogenesis of SuHx-PH in rat. <i>Conclusions:</i> Our results suggest that the HIF2α-dependent upregulation of SETDB1 facilitates hypoxia-induced functional and phenotypical changes of PMVECs, potentially contributing to the hypoxia-induced pulmonary vascular remodeling and PH.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
β3-adrenergic agonist counters oxidative stress and Na+-K+ pump inhibitory S-glutathionylation of placental cells: Implications for preeclampsia. β3-肾上腺素能激动剂可对抗胎盘细胞的氧化应激和 Na+-K+ 泵抑制性 S-谷胱甘肽化:对子痫前期的影响。
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1152/ajpcell.00379.2024
Chia-Chi Liu, Yunjia Zhang, Yeon Jae Kim, Elisha J Hamilton, Bei Xu, Jane Limas, Sharon McCracken, Jonathan M Morris, Angela Makris, Annemarie Hennessy, Helge H Rasmussen

Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by Na+-K+ pump inhibition and S-glutathionylation of its β1 subunit (GSS-β1), a modification that inhibits the pump. β3-adrenergic receptor (β3-AR) agonists can reverse GSS-β1. We examined effects of the agonist CL316,243 on GSS-β1 and sources of H/R-induced oxidative stress in immortalized first trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal term pregnancies. H/R increased GSS-β1 and, reflecting compromised α1/β1 subunit interaction, it reduced α1/β1 pump subunit co-immunoprecipitation. H/R increased p47phox/p22phox NADPH oxidase subunit co-immunoprecipitation reflecting membrane translocation of cytosolic p47phox that is needed to activate NADPH oxidase. Fluorescence of O2•--sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples NO synthesis towards synthesis of O2•- and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor α (TNF-α) increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-β1 and decreases of α1/β1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release and restored trophoblast integration in endothelial cell networks. H/R induced GSS-β1, α1/β1 subunit co-immunoprecipitation and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a β3-AR agonist counters key pathophysiological features of preeclampsia in vitro. β3 agonists already in human use for another purpose are potential candidates for re-purposing to treat preeclampsia.

子痫前期胎盘缺血/再灌注和缺氧/再氧合(H/R)引起的氧化应激伴随着Na+-K+泵抑制及其β1亚基(GSS-β1)的S-谷胱甘肽化,这种修饰可抑制该泵。β3-肾上腺素能受体(β3-AR)激动剂能逆转 GSS-β1。我们研究了激动剂 CL316,243 对 GSS-β1 的影响以及 H/R 诱导的氧化应激在永生化的人类前三个月滋养层细胞(HTR-8/SVneo)和从正常足月妊娠新鲜分离的胎盘外植体中的来源。H/R增加了GSS-β1,并减少了α1/β1泵亚基的共免疫沉淀,这反映了α1/β1亚基相互作用受到损害。H/R 增加了 p47phox/p22phox NADPH 氧化酶亚基的共沉淀,反映了激活 NADPH 氧化酶所需的细胞膜 p47phox 的膜转运。对 O2 敏感的二氢乙锭的荧光也同时增加。H/R增加了内皮一氧化氮合酶(GSS-eNOS)的S-谷胱甘肽化,从而解除了NO合成与O2合成的耦合,并减少了滋养细胞的迁移。肿瘤坏死因子α(TNF-α)诱导的氧化应激增加了可溶性fms样酪氨酸激酶受体1(sFlt-1)滋养细胞的释放(子痫前期的标志物),并减少了滋养细胞与内皮细胞网络的整合。CL316,243消除了H/R诱导的GSS-β1和α1/β1亚基共沉淀的减少,消除了NADPH氧化酶的激活和GSS-eNOS的增加,恢复了滋养细胞的迁移,消除了sFlt-1释放的增加,恢复了滋养细胞与内皮细胞网络的整合。H/R诱导的GSS-β1、α1/β1亚基共免疫沉淀和胎盘外植体的NADPH氧化酶活化反映了H/R对滋养层细胞的影响,而CL316,243消除了这些变化。我们得出的结论是,β3-AR 激动剂可在体外对抗子痫前期的主要病理生理特征。
{"title":"β3-adrenergic agonist counters oxidative stress and Na<sup>+</sup>-K<sup>+</sup> pump inhibitory S-glutathionylation of placental cells: Implications for preeclampsia.","authors":"Chia-Chi Liu, Yunjia Zhang, Yeon Jae Kim, Elisha J Hamilton, Bei Xu, Jane Limas, Sharon McCracken, Jonathan M Morris, Angela Makris, Annemarie Hennessy, Helge H Rasmussen","doi":"10.1152/ajpcell.00379.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00379.2024","url":null,"abstract":"<p><p>Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by Na<sup>+</sup>-K<sup>+</sup> pump inhibition and S-glutathionylation of its β1 subunit (GSS-β1), a modification that inhibits the pump. β3-adrenergic receptor (β3-AR) agonists can reverse GSS-β1. We examined effects of the agonist CL316,243 on GSS-β1 and sources of H/R-induced oxidative stress in immortalized first trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal term pregnancies. H/R increased GSS-β1 and, reflecting compromised α1/β1 subunit interaction, it reduced α1/β1 pump subunit co-immunoprecipitation. H/R increased p47<i><sup>phox</sup></i>/p22<i><sup>phox</sup></i> NADPH oxidase subunit co-immunoprecipitation reflecting membrane translocation of cytosolic p47<i><sup>phox</sup></i> that is needed to activate NADPH oxidase. Fluorescence of O<sub>2</sub><sup>•-</sup>-sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples NO synthesis towards synthesis of O<sub>2</sub><sup>•-</sup> and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor α (TNF-α) increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-β1 and decreases of α1/β1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release and restored trophoblast integration in endothelial cell networks. H/R induced GSS-β1, α1/β1 subunit co-immunoprecipitation and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a β3-AR agonist counters key pathophysiological features of preeclampsia in vitro. β3 agonists already in human use for another purpose are potential candidates for re-purposing to treat preeclampsia.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The fate of neuronal synapse homeostasis in aging, infection, and inflammation. 神经元突触平衡在衰老、感染和炎症中的命运。
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1152/ajpcell.00466.2024
Charlotte Tacke, Peter Landgraf, Daniela C Dieterich, Andrea Kröger

Neuroplasticity is the brain's ability to reorganize and modify its neuronal connections in response to environmental stimuli, experiences, learning, and disease processes. This encompasses a variety of mechanisms, including changes in synaptic strength and connectivity, the formation of new synapses, alterations in neuronal structure and function, and the generation of new neurons. Proper functioning of synapses, which facilitate neuron-to-neuron communication, is crucial for brain activity. Neuronal synapse homeostasis, which involves regulating and maintaining synaptic strength and function in the central nervous system (CNS), is vital for this process. Disruptions in synaptic balance, due to factors like inflammation, aging, or infection, can lead to impaired brain function. This review highlights the main aspects and mechanisms underlying synaptic homeostasis, particularly in the context of aging, infection, and inflammation.

神经可塑性是大脑根据环境刺激、经验、学习和疾病过程重组和改变神经元连接的能力。这包括多种机制,包括突触强度和连接性的变化、新突触的形成、神经元结构和功能的改变以及新神经元的生成。突触有助于神经元与神经元之间的交流,其正常功能对大脑活动至关重要。神经元突触平衡涉及调节和维持中枢神经系统(CNS)中的突触强度和功能,对这一过程至关重要。由于炎症、衰老或感染等因素造成的突触平衡破坏会导致大脑功能受损。本综述将重点介绍突触平衡的主要方面和机制,尤其是在衰老、感染和炎症的背景下。
{"title":"The fate of neuronal synapse homeostasis in aging, infection, and inflammation.","authors":"Charlotte Tacke, Peter Landgraf, Daniela C Dieterich, Andrea Kröger","doi":"10.1152/ajpcell.00466.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00466.2024","url":null,"abstract":"<p><p>Neuroplasticity is the brain's ability to reorganize and modify its neuronal connections in response to environmental stimuli, experiences, learning, and disease processes. This encompasses a variety of mechanisms, including changes in synaptic strength and connectivity, the formation of new synapses, alterations in neuronal structure and function, and the generation of new neurons. Proper functioning of synapses, which facilitate neuron-to-neuron communication, is crucial for brain activity. Neuronal synapse homeostasis, which involves regulating and maintaining synaptic strength and function in the central nervous system (CNS), is vital for this process. Disruptions in synaptic balance, due to factors like inflammation, aging, or infection, can lead to impaired brain function. This review highlights the main aspects and mechanisms underlying synaptic homeostasis, particularly in the context of aging, infection, and inflammation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A bovine model of hypoxia-induced pulmonary hypertension reveals a gradient of immune and matrisome response with a complement signature found in circulation. 缺氧诱发肺动脉高压的牛模型揭示了免疫和母体反应的梯度,在循环中发现了补体特征。
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1152/ajpcell.00274.2024
Jason Williams, Franklyn N Iheagwam, Sean P Maroney, Lauren R Schmitt, R Dale Brown, Greta M Krafsur, Maria G Frid, Maxwell C McCabe, Aneta Gandjeva, Kurt J Williams, James P Luyendyk, Anthony J Saviola, Rubin M Tuder, Kurt Stenmark, Kirk C Hansen

Pulmonary hypertension (PH) is a progressive vascular disease characterized by vascular remodeling, stiffening, and luminal obstruction, driven by dysregulated cell proliferation, inflammation, and extracellular matrix (ECM) alterations. Despite the recognized contribution of ECM dysregulation to PH pathogenesis, the precise molecular alterations in the matrisome remain poorly understood. In this study, we employed a matrisome-focused proteomics approach to map the protein composition in a young bovine calf model of acute hypoxia-induced PH. Our findings reveal distinct alterations in the matrisome along the pulmonary vascular axis, with the most prominent changes observed in the main pulmonary artery. Key alterations included a strong immune response and wound repair signature, characterized by increased levels of complement components, coagulation cascade proteins, and provisional matrix markers. Additionally, we observed upregulation of ECM-modifying enzymes, growth factors, and core ECM proteins implicated in vascular stiffening, such as collagens, periostin, tenacsin-C, and fibrin(ogen). Notably, these alterations correlated with increased mean pulmonary arterial pressure and vascular remodeling. In the plasma, we identified increased levels of complement components, indicating a systemic inflammatory response accompanying the vascular remodeling. Our findings shed light on the dynamic matrisome remodeling in early-stage PH, implicating a wound-healing trajectory with distinct patterns from the MPA to the distal vasculature. This study provides novel insights into the molecular underpinnings of PH pathogenesis and highlights potential biomarkers and therapeutic targets within the matrisome landscape.

肺动脉高压(PH)是一种进行性血管疾病,以血管重塑、硬化和管腔阻塞为特征,由失调的细胞增殖、炎症和细胞外基质(ECM)改变驱动。尽管 ECM 失调在 PH 发病机制中的作用已得到公认,但人们对基质组的确切分子变化仍然知之甚少。在这项研究中,我们采用了一种以基质组为重点的蛋白质组学方法来绘制急性缺氧诱导的 PH 幼牛模型的蛋白质组成图。我们的研究结果表明,沿着肺血管轴的基质组发生了明显的变化,其中主肺动脉的变化最为显著。主要的改变包括强烈的免疫反应和伤口修复特征,其特征是补体成分、凝血级联蛋白和临时基质标记物水平的升高。此外,我们还观察到 ECM 修饰酶、生长因子和与血管硬化有关的核心 ECM 蛋白(如胶原、骨膜增生蛋白、tenacsin-C 和纤维蛋白)的上调。值得注意的是,这些变化与平均肺动脉压升高和血管重塑有关。在血浆中,我们发现补体成分水平升高,这表明血管重塑伴随着全身炎症反应。我们的发现揭示了 PH 早期动态的基质组重塑,暗示了从 MPA 到远端血管具有不同模式的伤口愈合轨迹。这项研究提供了有关 PH 发病机制分子基础的新见解,并强调了基质组景观中潜在的生物标记物和治疗靶点。
{"title":"A bovine model of hypoxia-induced pulmonary hypertension reveals a gradient of immune and matrisome response with a complement signature found in circulation.","authors":"Jason Williams, Franklyn N Iheagwam, Sean P Maroney, Lauren R Schmitt, R Dale Brown, Greta M Krafsur, Maria G Frid, Maxwell C McCabe, Aneta Gandjeva, Kurt J Williams, James P Luyendyk, Anthony J Saviola, Rubin M Tuder, Kurt Stenmark, Kirk C Hansen","doi":"10.1152/ajpcell.00274.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00274.2024","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a progressive vascular disease characterized by vascular remodeling, stiffening, and luminal obstruction, driven by dysregulated cell proliferation, inflammation, and extracellular matrix (ECM) alterations. Despite the recognized contribution of ECM dysregulation to PH pathogenesis, the precise molecular alterations in the matrisome remain poorly understood. In this study, we employed a matrisome-focused proteomics approach to map the protein composition in a young bovine calf model of acute hypoxia-induced PH. Our findings reveal distinct alterations in the matrisome along the pulmonary vascular axis, with the most prominent changes observed in the main pulmonary artery. Key alterations included a strong immune response and wound repair signature, characterized by increased levels of complement components, coagulation cascade proteins, and provisional matrix markers. Additionally, we observed upregulation of ECM-modifying enzymes, growth factors, and core ECM proteins implicated in vascular stiffening, such as collagens, periostin, tenacsin-C, and fibrin(ogen). Notably, these alterations correlated with increased mean pulmonary arterial pressure and vascular remodeling. In the plasma, we identified increased levels of complement components, indicating a systemic inflammatory response accompanying the vascular remodeling. Our findings shed light on the dynamic matrisome remodeling in early-stage PH, implicating a wound-healing trajectory with distinct patterns from the MPA to the distal vasculature. This study provides novel insights into the molecular underpinnings of PH pathogenesis and highlights potential biomarkers and therapeutic targets within the matrisome landscape.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diabetes induces modifications in costameric proteins and increases cardiomyocyte stiffness. 糖尿病会诱导成本层蛋白的改变,并增加心肌细胞的硬度。
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-07 DOI: 10.1152/ajpcell.00273.2024
Gerardo Romanelli, Lihuén Villarreal, Camila Espasandín, Juan Claudio Benech

Several studies have demonstrated that diabetes mellitus can increase the risk of cardiovascular disease and remains the principal cause of death in these patients. Costameres connect the sarcolemma with the cytoskeleton and extracellular matrix, facilitating the transmission of mechanical forces and cell signaling. They are related to cardiac physiology because individual cardiac cells are connected by intercalated discs that synchronize muscle contraction. Diabetes impacts the nanomechanical properties of cardiomyocytes, resulting in increased cellular and left ventricular stiffness, as evidenced in clinical studies of these patients. The question of whether costameric proteins are affected by diabetes in the heart has not been studied. This work analyzes whether type 1 diabetes mellitus (T1DM) modifies the costameric proteins and coincidentally changes the cellular mechanics in the same cardiomyocytes. The samples were analyzed by immunotechniques using laser confocal microscopy. Significant statistical differences were found in the spatial arrangement of the costameric proteins. However, these differences are not due to their expression. Atomic force microscopy was used to compare intrinsic cellular stiffness between diabetic and normal cardiomyocytes and obtain the first elasticity map sections of diabetic living cardiomyocytes. Data obtained demonstrated that diabetic cardiomyocytes had higher stiffness than control. The present work shows experimental evidence that intracellular changes related to cell-cell and cell-extracellular matrix communication occur, which could be related to cardiac pathogenic mechanisms. These changes could contribute to alterations in the mechanical and electrical properties of cardiomyocytes and, consequently, to diabetic cardiomyopathy.NEW & NOTEWORTHY The structural organization of cardiomyocyte proteins is critical for their efficient functioning as a contractile unit in the heart. This work shows that diabetes mellitus induces significant changes in the spatial organization of costamere proteins, t tubules, and intercalated discs. We obtained the first elasticity map sections of living diabetic cardiomyocytes. The results show statistical differences in the map sections of diabetic and control cardiomyocytes, with diabetic cardiomyocytes being stiffer than normal ones.

多项研究表明,糖尿病会增加罹患心血管疾病的风险,并且仍然是这些患者死亡的主要原因。肋膜将肌浆与细胞骨架和细胞外基质连接起来,促进了机械力和细胞信号的传递。它们与心脏生理学有关,因为单个心脏细胞由可同步肌肉收缩的闰盘连接。糖尿病会影响心肌细胞的纳米机械特性,导致细胞和左心室硬度增加,对这些患者的临床研究就证明了这一点。至于心脏中的 Costameric 蛋白是否会受到糖尿病的影响,目前还没有研究。这项研究分析了 T1DM 是否会改变成本层蛋白,并巧合地改变相同心肌细胞的细胞力学。样本通过激光共聚焦显微镜的免疫技术进行分析。结果表明,心肌细胞中的共价键蛋白在空间排列上存在显著的统计学差异。然而,这些差异并不是由于它们的表达所致。利用原子力显微镜比较了糖尿病和正常心肌细胞的内在细胞硬度,并首次获得了糖尿病活体心肌细胞的弹性图切片。获得的数据表明,糖尿病心肌细胞的硬度高于对照组。本研究通过实验证明,细胞内发生了与细胞-细胞和细胞-细胞外基质沟通有关的变化,这些变化可能与心脏致病机制有关。这些变化可能会导致心肌细胞机械和电特性的改变,进而引发糖尿病心肌病。
{"title":"Diabetes induces modifications in costameric proteins and increases cardiomyocyte stiffness.","authors":"Gerardo Romanelli, Lihuén Villarreal, Camila Espasandín, Juan Claudio Benech","doi":"10.1152/ajpcell.00273.2024","DOIUrl":"10.1152/ajpcell.00273.2024","url":null,"abstract":"<p><p>Several studies have demonstrated that diabetes mellitus can increase the risk of cardiovascular disease and remains the principal cause of death in these patients. Costameres connect the sarcolemma with the cytoskeleton and extracellular matrix, facilitating the transmission of mechanical forces and cell signaling. They are related to cardiac physiology because individual cardiac cells are connected by intercalated discs that synchronize muscle contraction. Diabetes impacts the nanomechanical properties of cardiomyocytes, resulting in increased cellular and left ventricular stiffness, as evidenced in clinical studies of these patients. The question of whether costameric proteins are affected by diabetes in the heart has not been studied. This work analyzes whether type 1 diabetes mellitus (T1DM) modifies the costameric proteins and coincidentally changes the cellular mechanics in the same cardiomyocytes. The samples were analyzed by immunotechniques using laser confocal microscopy. Significant statistical differences were found in the spatial arrangement of the costameric proteins. However, these differences are not due to their expression. Atomic force microscopy was used to compare intrinsic cellular stiffness between diabetic and normal cardiomyocytes and obtain the first elasticity map sections of diabetic living cardiomyocytes. Data obtained demonstrated that diabetic cardiomyocytes had higher stiffness than control. The present work shows experimental evidence that intracellular changes related to cell-cell and cell-extracellular matrix communication occur, which could be related to cardiac pathogenic mechanisms. These changes could contribute to alterations in the mechanical and electrical properties of cardiomyocytes and, consequently, to diabetic cardiomyopathy.<b>NEW & NOTEWORTHY</b> The structural organization of cardiomyocyte proteins is critical for their efficient functioning as a contractile unit in the heart. This work shows that diabetes mellitus induces significant changes in the spatial organization of costamere proteins, <i>t</i> tubules, and intercalated discs. We obtained the first elasticity map sections of living diabetic cardiomyocytes. The results show statistical differences in the map sections of diabetic and control cardiomyocytes, with diabetic cardiomyocytes being stiffer than normal ones.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CD8+ tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis. CD8+组织驻留记忆T细胞对博莱霉素诱导的肺纤维化至关重要
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-09 DOI: 10.1152/ajpcell.00368.2024
Xiao Feng, Fan Yu, Xin-Liang He, Pei-Pei Cheng, Qian Niu, Li-Qin Zhao, Qian Li, Xiao-Lin Cui, Zi-Heng Jia, Shu-Yi Ye, Li-Mei Liang, Lin-Jie Song, Liang Xiong, Fei Xiang, Xiaorong Wang, Wan-Li Ma, Hong Ye

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patients. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, the adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with chemokine CC-motif ligand (CCL18) induced CD8+ TRM cell expansion and exacerbated fibrosis, whereas blocking C-C chemokine receptor 8 (CCR8) prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach. NEW & NOTEWORTHY The role of CD8+ TRM cells in the development of pulmonary fibrosis was validated and studied in the classic model of pulmonary fibrosis. It was proposed for the first time that CCL18 has a chemotactic effect on CD8+ TRM cells, thereby exacerbating pulmonary fibrosis.

人体组织驻留记忆 T 细胞(TRM)在保护机体免受感染和癌症侵害方面发挥着至关重要的作用。最近的研究发现,特发性肺纤维化患者肺组织中的TRM细胞数量有所增加。然而,TRM细胞在肺纤维化中的功能性后果仍不清楚。在这里,我们发现在博莱霉素诱导的肺纤维化小鼠肺中,TRM细胞,尤其是CD8+亚群的数量有所增加。增加或减少小鼠肺中的CD8+TRM细胞可相应地改变肺纤维化的严重程度。此外,从肺纤维化小鼠肺中收养转移含有大量CD8+TRM细胞的CD8+T细胞足以诱导对照组小鼠肺纤维化。用CCL18处理可诱导CD8+TRM细胞扩增并加剧肺纤维化,而阻断CCR8可阻止CD8+TRM招募并抑制肺纤维化。总之,CD8+ TRM细胞对博莱霉素诱导的肺纤维化至关重要,靶向CCL18/CCR8/CD8+ TRM细胞可能是一种潜在的治疗方法。
{"title":"CD8<sup>+</sup> tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis.","authors":"Xiao Feng, Fan Yu, Xin-Liang He, Pei-Pei Cheng, Qian Niu, Li-Qin Zhao, Qian Li, Xiao-Lin Cui, Zi-Heng Jia, Shu-Yi Ye, Li-Mei Liang, Lin-Jie Song, Liang Xiong, Fei Xiang, Xiaorong Wang, Wan-Li Ma, Hong Ye","doi":"10.1152/ajpcell.00368.2024","DOIUrl":"10.1152/ajpcell.00368.2024","url":null,"abstract":"<p><p>Human tissue-resident memory T (T<sub>RM</sub>) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of T<sub>RM</sub> cells in the lung tissues of idiopathic pulmonary fibrosis patients. However, the functional consequences of T<sub>RM</sub> cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of T<sub>RM</sub> cells, especially the CD8<sup>+</sup> subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8<sup>+</sup> T<sub>RM</sub> cells in mouse lungs accordingly altered the severity of fibrosis. In addition, the adoptive transfer of CD8<sup>+</sup> T cells containing a large number of CD8<sup>+</sup> T<sub>RM</sub> cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with chemokine CC-motif ligand (CCL18) induced CD8<sup>+</sup> T<sub>RM</sub> cell expansion and exacerbated fibrosis, whereas blocking C-C chemokine receptor 8 (CCR8) prevented CD8<sup>+</sup> T<sub>RM</sub> recruitment and inhibited pulmonary fibrosis. In conclusion, CD8<sup>+</sup> T<sub>RM</sub> cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8<sup>+</sup> T<sub>RM</sub> cells may be a potential therapeutic approach. <b>NEW & NOTEWORTHY</b> The role of CD8<sup>+</sup> T<sub>RM</sub> cells in the development of pulmonary fibrosis was validated and studied in the classic model of pulmonary fibrosis. It was proposed for the first time that CCL18 has a chemotactic effect on CD8<sup>+</sup> T<sub>RM</sub> cells, thereby exacerbating pulmonary fibrosis.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Physical effects of 3-D microenvironments on confined cell behaviors. 三维微环境对封闭细胞行为的物理影响
IF 5 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-09 DOI: 10.1152/ajpcell.00288.2024
Bao-Qiong Lan, Ya-Jun Wang, Sai-Xi Yu, Wei Liu, Yan-Jun Liu

Cell migration is a fundamental and functional cellular process, influenced by a complex microenvironment consisting of different cells and extracellular matrix. Recent research has highlighted that, besides biochemical cues from the microenvironment, physical cues can also greatly alter cellular behavior. However, due to the complexity of the microenvironment, little is known about how the physical interactions between migrating cells and surrounding microenvironment instructs cell movement. Here, we explore various examples of three-dimensional microenvironment reconstruction models in vitro and describe how the physical interplay between migrating cells and the neighboring microenvironment controls cell behavior. Understanding this mechanical cooperation will provide key insights into organ development, regeneration, and tumor metastasis.

细胞迁移是一个基本的功能性细胞过程,受到由不同细胞和细胞外基质(ECM)组成的复杂微环境的影响。最近的研究突出表明,除了来自微环境的生化线索外,物理线索也能在很大程度上改变细胞的行为。然而,由于微环境的复杂性,人们对迁移细胞与周围微环境之间的物理相互作用如何指导细胞运动知之甚少。在这里,我们探讨了体外三维微环境重建模型的各种实例,并描述了迁移细胞与邻近微环境之间的物理相互作用是如何控制细胞行为的。了解这种机械合作将为器官发育、再生和肿瘤转移提供重要的启示。
{"title":"Physical effects of 3-D microenvironments on confined cell behaviors.","authors":"Bao-Qiong Lan, Ya-Jun Wang, Sai-Xi Yu, Wei Liu, Yan-Jun Liu","doi":"10.1152/ajpcell.00288.2024","DOIUrl":"10.1152/ajpcell.00288.2024","url":null,"abstract":"<p><p>Cell migration is a fundamental and functional cellular process, influenced by a complex microenvironment consisting of different cells and extracellular matrix. Recent research has highlighted that, besides biochemical cues from the microenvironment, physical cues can also greatly alter cellular behavior. However, due to the complexity of the microenvironment, little is known about how the physical interactions between migrating cells and surrounding microenvironment instructs cell movement. Here, we explore various examples of three-dimensional microenvironment reconstruction models in vitro and describe how the physical interplay between migrating cells and the neighboring microenvironment controls cell behavior. Understanding this mechanical cooperation will provide key insights into organ development, regeneration, and tumor metastasis.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
American journal of physiology. Cell physiology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1