Tissue & cell最新文献_第9页

In vitro osteogenic potential of magnesium alloy without and with calcium phosphate coating 磷酸钙包覆和未包覆镁合金的体外成骨潜能。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-29 DOI: 10.1016/j.tice.2025.103256

Mariana de Oliveira Viana Veras , Fátima Regina Nunes de Sousa , Conceição Silva Martins , Gildênio Estevam Freire , Ana Beatriz Graça Duarte , Thâmara Manoela Marinho Bezerra , Yves Ramos Costa Beviláqua , Stephany Ellen de Castro , Matheus Brandão dos Santos Lopes , Rosemayre Souza Freire , Pierre Basílio Almeida Fechine , Abrahão Cavalcante Gomes de Souza Carvalho , Paula Goes , Mirna Marques Bezerra , Renata Ferreira Carvalho Leitão

Magnesium-based biomaterials have emerged as promising candidates for bone regeneration due to their biodegradability and favorable mechanical properties. This study investigated the effects of Magnesium alloys without (Mg1) and with (Mg2) calcium phosphate coating on osteoblast viability and activation. The physical structure of the alloys was analyzed by surface characterization, mechanical testing, and biodegradation assays. Biological performance was evaluated through MTT and MTS assays for cell viability and proliferation, quantification of alkaline phosphatase activity at 24 h, 7, and 15 days, and mineralization by Von Kossa staining, after 21 days. Cell morphology and apoptosis were assessed using fluorescence microscopy and immunostaining for caspase 3 and 9, while protein expression of BMP-2, OPG, and RANK-L was also investigated by immunostaining. The results demonstrated a significant increase in viable cells in both Mg1 and Mg2 groups after 24 and 48 h. Enhanced mineralization and a significant increase in alkaline phosphatase activity were observed in the Mg2 group. Both Mg1 and Mg2 groups exhibited a similar reduction in caspases 3 and 9 expression, indicating cell survival despite morphological changes. Furthermore, osteoblasts cultured on both alloys showed greater expression of BMP-2 and OPG, compared to the DMEM group. Taken together, these findings highlight the potential of calcium phosphate-coated magnesium alloy as a novel approach for bone restoration in the future.

镁基生物材料由于其生物可降解性和良好的力学性能而成为骨再生的有希望的候选材料。研究了未包覆（Mg1）和包覆（Mg2）磷酸钙的镁合金对成骨细胞活力和活化的影响。通过表面表征、力学测试和生物降解试验分析了合金的物理结构。通过MTT和MTS测定细胞活力和增殖，测定24 h、7和15天的碱性磷酸酶活性，并在21天后通过Von Kossa染色矿化来评估生物性能。采用荧光显微镜和caspase 3、caspase 9免疫染色法观察细胞形态和凋亡情况，采用免疫染色法观察BMP-2、OPG、RANK-L蛋白表达。结果显示，24和48 h后，Mg1和Mg2组的活细胞显著增加。Mg2组矿化度增强，碱性磷酸酶活性显著升高。Mg1和Mg2组caspases 3和caspases 9的表达都出现了类似的减少，表明尽管形态发生了变化，但细胞存活了下来。此外，与DMEM组相比，两种合金培养的成骨细胞BMP-2和OPG的表达均较高。综上所述，这些发现突出了磷酸钙包覆镁合金作为未来骨修复新方法的潜力。

{"title":"In vitro osteogenic potential of magnesium alloy without and with calcium phosphate coating","authors":"Mariana de Oliveira Viana Veras , Fátima Regina Nunes de Sousa , Conceição Silva Martins , Gildênio Estevam Freire , Ana Beatriz Graça Duarte , Thâmara Manoela Marinho Bezerra , Yves Ramos Costa Beviláqua , Stephany Ellen de Castro , Matheus Brandão dos Santos Lopes , Rosemayre Souza Freire , Pierre Basílio Almeida Fechine , Abrahão Cavalcante Gomes de Souza Carvalho , Paula Goes , Mirna Marques Bezerra , Renata Ferreira Carvalho Leitão","doi":"10.1016/j.tice.2025.103256","DOIUrl":"10.1016/j.tice.2025.103256","url":null,"abstract":"<div><div>Magnesium-based biomaterials have emerged as promising candidates for bone regeneration due to their biodegradability and favorable mechanical properties. This study investigated the effects of Magnesium alloys without (Mg1) and with (Mg2) calcium phosphate coating on osteoblast viability and activation. The physical structure of the alloys was analyzed by surface characterization, mechanical testing, and biodegradation assays. Biological performance was evaluated through MTT and MTS assays for cell viability and proliferation, quantification of alkaline phosphatase activity at 24 h, 7, and 15 days, and mineralization by Von Kossa staining, after 21 days. Cell morphology and apoptosis were assessed using fluorescence microscopy and immunostaining for caspase 3 and 9, while protein expression of BMP-2, OPG, and RANK-L was also investigated by immunostaining. The results demonstrated a significant increase in viable cells in both Mg1 and Mg2 groups after 24 and 48 h. Enhanced mineralization and a significant increase in alkaline phosphatase activity were observed in the Mg2 group. Both Mg1 and Mg2 groups exhibited a similar reduction in caspases 3 and 9 expression, indicating cell survival despite morphological changes. Furthermore, osteoblasts cultured on both alloys showed greater expression of BMP-2 and OPG, compared to the DMEM group. Taken together, these findings highlight the potential of calcium phosphate-coated magnesium alloy as a novel approach for bone restoration in the future.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103256"},"PeriodicalIF":2.5,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Core regulatory mechanisms of macrophage dynamic polarization and multicellular interaction networks in driving venous thromboembolism 巨噬细胞动态极化和多细胞相互作用网络驱动静脉血栓栓塞的核心调控机制

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-28 DOI: 10.1016/j.tice.2025.103252

Yi Liu , Yong Zeng , Mingyan Zhu , Changlong Cui , Lin Liao

Venous thromboembolism (VTE) is one of the leading causes of cardiovascular-related mortality worldwide. Its pathogenesis is complex, and current treatment strategies centered on anticoagulation face challenges such as high bleeding risks and limited efficacy in dissolving established thrombi. In recent years, research in the field of VTE has increasingly focused on the "inflammation-thrombosis" interaction, with macrophages emerging as a central regulator in this process, highlighting the growing importance of related studies. Through dynamic phenotypic polarization into pro-inflammatory M1 and anti-inflammatory M2 states, macrophages contribute to both thrombus formation and resolution. In the early stages of thrombogenesis, M1 macrophages establish a pro-inflammatory milieu by secreting chemokines, promoting leukocyte infiltration, enhancing platelet activation, and facilitating fibrin deposition, ultimately contributing to thrombus stabilization. Conversely, M2 macrophages play a central role in thrombus resolution by secreting matrix metalloproteinases (MMPs) and cytokines that promote fibrinolysis and endothelial repair. These polarization states are tightly regulated by hypoxia, metabolic reprogramming, and intercellular signals from endothelial cells, platelets, and neutrophils, forming an intricate multicellular regulatory network. Additionally, macrophages engage in exosome-mediated communication and immunomodulation, further amplifying thrombus-associated inflammation and vascular remodeling. Targeting macrophage polarization—particularly enhancing the M2 phenotype or disrupting chemotactic signaling pathways—has shown promise in reducing thrombus burden in preclinical models. Understanding the spatial-temporal heterogeneity of macrophage subsets and their interactions with other cell types may uncover novel therapeutic targets. This review summarizes current advances in macrophage biology in VTE, emphasizing their dual functional roles and regulatory networks. A better understanding of macrophage-driven immune-thrombotic crosstalk holds potential to refine current treatments beyond anticoagulation and to develop precision immunotherapies for VTE.

静脉血栓栓塞（VTE）是全球心血管相关死亡的主要原因之一。其发病机制复杂，目前以抗凝治疗为中心的治疗策略面临着出血风险高、溶栓效果有限等挑战。近年来，VTE领域的研究越来越关注“炎症-血栓”的相互作用，巨噬细胞在这一过程中作为中枢调节因子出现，相关研究的重要性日益凸显。巨噬细胞通过动态表型极化进入促炎M1和抗炎M2状态，参与血栓形成和溶解。在血栓形成早期，M1巨噬细胞通过分泌趋化因子，促进白细胞浸润，增强血小板活化，促进纤维蛋白沉积，建立促炎环境，最终促进血栓稳定。相反，M2巨噬细胞通过分泌基质金属蛋白酶（MMPs）和促进纤维蛋白溶解和内皮修复的细胞因子，在血栓溶解中发挥核心作用。这些极化状态受到缺氧、代谢重编程和内皮细胞、血小板和中性粒细胞的细胞间信号的严格调节，形成了一个复杂的多细胞调节网络。此外，巨噬细胞参与外泌体介导的通讯和免疫调节，进一步放大血栓相关的炎症和血管重塑。靶向巨噬细胞极化-特别是增强M2表型或破坏趋化信号通路-在临床前模型中显示出减少血栓负担的希望。了解巨噬细胞亚群的时空异质性及其与其他细胞类型的相互作用可能会发现新的治疗靶点。本文综述了巨噬细胞在静脉血栓栓塞中的生物学研究进展，重点介绍了巨噬细胞的双重功能作用和调控网络。更好地了解巨噬细胞驱动的免疫-血栓形成串扰，有可能改进目前的治疗方法，而不仅仅是抗凝治疗，并开发精确的静脉血栓栓塞免疫疗法。

{"title":"Core regulatory mechanisms of macrophage dynamic polarization and multicellular interaction networks in driving venous thromboembolism","authors":"Yi Liu , Yong Zeng , Mingyan Zhu , Changlong Cui , Lin Liao","doi":"10.1016/j.tice.2025.103252","DOIUrl":"10.1016/j.tice.2025.103252","url":null,"abstract":"<div><div>Venous thromboembolism (VTE) is one of the leading causes of cardiovascular-related mortality worldwide. Its pathogenesis is complex, and current treatment strategies centered on anticoagulation face challenges such as high bleeding risks and limited efficacy in dissolving established thrombi. In recent years, research in the field of VTE has increasingly focused on the \"inflammation-thrombosis\" interaction, with macrophages emerging as a central regulator in this process, highlighting the growing importance of related studies. Through dynamic phenotypic polarization into pro-inflammatory M1 and anti-inflammatory M2 states, macrophages contribute to both thrombus formation and resolution. In the early stages of thrombogenesis, M1 macrophages establish a pro-inflammatory milieu by secreting chemokines, promoting leukocyte infiltration, enhancing platelet activation, and facilitating fibrin deposition, ultimately contributing to thrombus stabilization. Conversely, M2 macrophages play a central role in thrombus resolution by secreting matrix metalloproteinases (MMPs) and cytokines that promote fibrinolysis and endothelial repair. These polarization states are tightly regulated by hypoxia, metabolic reprogramming, and intercellular signals from endothelial cells, platelets, and neutrophils, forming an intricate multicellular regulatory network. Additionally, macrophages engage in exosome-mediated communication and immunomodulation, further amplifying thrombus-associated inflammation and vascular remodeling. Targeting macrophage polarization—particularly enhancing the M2 phenotype or disrupting chemotactic signaling pathways—has shown promise in reducing thrombus burden in preclinical models. Understanding the spatial-temporal heterogeneity of macrophage subsets and their interactions with other cell types may uncover novel therapeutic targets. This review summarizes current advances in macrophage biology in VTE, emphasizing their dual functional roles and regulatory networks. A better understanding of macrophage-driven immune-thrombotic crosstalk holds potential to refine current treatments beyond anticoagulation and to develop precision immunotherapies for VTE.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103252"},"PeriodicalIF":2.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Qingyu formula inhibits ferroptosis in HK-2 cells and in a diabetic nephropathy mouse model via the Nrf2/SLC7A11/GPX4 pathway 清瘀方通过Nrf2/SLC7A11/GPX4途径抑制HK-2细胞和糖尿病肾病小鼠模型中的铁下垂。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-28 DOI: 10.1016/j.tice.2025.103236

Jie Liu , Yuan-Yuan Xu , Tian-Ye Gao

Background

Diabetic kidney disease (DKD) is a severe microvascular complication, and ferroptosis is a major contributor to its pathogenesis. This study investigated the protective effects of Qingyu formula (QYF), a traditional Chinese medicine prescription, against ferroptosis in high glucose-induced renal injury.

Methods

In vitro, human renal tubular cells (human kidney 2 [HK-2]) under high glucose conditions were treated with QYF. In vivo, the induced diabetic mice received QYF interventions. Biochemical and molecular assays assessed cell viability, oxidative stress, ferroptosis markers (Fe²⁺, glutathione [GSH], malondialdehyde) and nuclear factor erythroid 2-related factor 2/solute carrier family 7 member 11/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) pathway activity.

Results

Qingyu formula enhanced cell viability and reduced reactive oxygen species in high glucose-treated HK-2 cells. It mitigated ferroptosis by decreasing Fe²⁺ accumulation and increasing GSH levels both in vivo and in vitro. Mechanistically, QYF upregulated GPX4, Nrf2 and SLC7A11. In diabetic mice, it improved metabolic parameters and reduced proteinuria in a dose-dependent manner, with high doses showing efficacy similar to that of clinically used irbesartan.

Conclusions

Qingyu formula protects against high glucose-induced renal injury by suppressing ferroptosis via the activation of the Nrf2/SLC7A11/GPX4 pathway. These findings support QYF as a promising candidate for targeting ferroptosis in DKD. Future studies should identify its active constituents and evaluate its efficacy in clinical trials.

背景：糖尿病肾病（DKD）是一种严重的微血管并发症，而铁下垂是其发病机制的主要因素。研究中药清瘀方对高糖肾损伤大鼠铁下垂的保护作用。方法：在体外以高糖条件下的人肾小管细胞（human kidney 2 [HK-2]）处理。在体内，诱导的糖尿病小鼠接受QYF干预。生化和分子检测评估细胞活力、氧化应激、铁死亡标志物（Fe 2 +、谷胱甘肽[GSH]、丙二醛）和核因子红系2相关因子2/溶质载体家族7成员11/谷胱甘肽过氧化物酶4 （Nrf2/SLC7A11/GPX4）途径活性。结果：清瘀方提高高糖处理的HK-2细胞活力，降低活性氧。它通过减少体内和体外的Fe 2 +积累和增加GSH水平来减轻铁下垂。在机制上，QYF上调GPX4、Nrf2和SLC7A11。在糖尿病小鼠中，它以剂量依赖的方式改善代谢参数并减少蛋白尿，高剂量的效果与临床使用的厄贝沙坦相似。结论：清瘀方通过激活Nrf2/SLC7A11/GPX4通路抑制铁上沉，对高糖所致肾损伤具有保护作用。这些发现支持QYF作为一种有希望的靶向DKD铁下垂的候选药物。未来的研究应确定其有效成分，并在临床试验中评估其疗效。

{"title":"Qingyu formula inhibits ferroptosis in HK-2 cells and in a diabetic nephropathy mouse model via the Nrf2/SLC7A11/GPX4 pathway","authors":"Jie Liu , Yuan-Yuan Xu , Tian-Ye Gao","doi":"10.1016/j.tice.2025.103236","DOIUrl":"10.1016/j.tice.2025.103236","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic kidney disease (DKD) is a severe microvascular complication, and ferroptosis is a major contributor to its pathogenesis. This study investigated the protective effects of Qingyu formula (QYF), a traditional Chinese medicine prescription, against ferroptosis in high glucose-induced renal injury.</div></div><div><h3>Methods</h3><div>In vitro, human renal tubular cells (human kidney 2 [HK-2]) under high glucose conditions were treated with QYF. In vivo, the induced diabetic mice received QYF interventions. Biochemical and molecular assays assessed cell viability, oxidative stress, ferroptosis markers (Fe²⁺, glutathione [GSH], malondialdehyde) and nuclear factor erythroid 2-related factor 2/solute carrier family 7 member 11/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) pathway activity.</div></div><div><h3>Results</h3><div>Qingyu formula enhanced cell viability and reduced reactive oxygen species in high glucose-treated HK-2 cells. It mitigated ferroptosis by decreasing Fe²⁺ accumulation and increasing GSH levels both in vivo and in vitro. Mechanistically, QYF upregulated GPX4, Nrf2 and SLC7A11. In diabetic mice, it improved metabolic parameters and reduced proteinuria in a dose-dependent manner, with high doses showing efficacy similar to that of clinically used irbesartan.</div></div><div><h3>Conclusions</h3><div>Qingyu formula protects against high glucose-induced renal injury by suppressing ferroptosis via the activation of the Nrf2/SLC7A11/GPX4 pathway. These findings support QYF as a promising candidate for targeting ferroptosis in DKD. Future studies should identify its active constituents and evaluate its efficacy in clinical trials.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103236"},"PeriodicalIF":2.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

KAT2A accelerates lung cancer progression through succinylation of TGFβR2 KAT2A通过TGFβR2琥珀酰化加速肺癌进展。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-28 DOI: 10.1016/j.tice.2025.103254

Mingqiang Shen , Qingqing Sun , Jinjiao Zhang , Tengfang Zhang , Lei Zhang

Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is one of the leading causes of cancer-related mortality worldwide. Succinylation has been implicated in the pathogenesis of NSCLC at the molecular level. The succinyltransferase lysine acetyltransferase 2 A (KAT2A) exhibits oncogenic properties in diverse cancers; however, its role in NSCLC development remains unclear. This study employed bioinformatics techniques, clinical specimens, and NSCLC cell lines to analyze KAT2A expression. Cell malignancy was assessed using the cell counting kit-8 (CCK-8) and colony-formation assays. Glycolytic activity was evaluated by measuring glucose uptake, lactate production, extracellular acidification rate, and oxygen consumption rate. The underlying mechanisms were explored using quantitative real-time polymerase chain reaction, immunoblotting, immunoprecipitation, immunofluorescence, and cycloheximide chase assays. The results showed that KAT2A expression was notably higher in NSCLC and was linked to poor prognosis. Knockdown of KAT2A suppressed NSCLC cell growth and glycolysis. Mechanistically, KAT2A knockdown reduced the succinylation of transforming growth factor beta receptor 2 (TGFβR2) at lysine 493, leading to decreased expression of TGFβR2. A mutation at this site attenuated the oncogenic and glycolytic effects induced by TGFβR2 overexpression. Moreover, in vivo experiments demonstrated that KAT2A knockdown markedly inhibited tumor growth. Our findings suggest that KAT2A functions as an oncogenic driver in NSCLC by modulating the succinylation of TGFβR2, underscoring its potential as a therapeutic target.

非小细胞肺癌（NSCLC）是肺癌的一个主要亚型，是全球癌症相关死亡的主要原因之一。琥珀酰化在分子水平上与非小细胞肺癌的发病机制有关。琥珀基转移酶赖氨酸乙酰转移酶2 A （KAT2A）在多种癌症中表现出致癌特性；然而，其在非小细胞肺癌发展中的作用尚不清楚。本研究采用生物信息学技术、临床标本和NSCLC细胞系分析KAT2A的表达。使用细胞计数试剂盒-8 （CCK-8）和集落形成试验评估细胞恶性。糖酵解活性通过测量葡萄糖摄取、乳酸生成、细胞外酸化速率和氧气消耗速率来评估。利用实时定量聚合酶链反应、免疫印迹、免疫沉淀、免疫荧光和环己亚胺追踪法探索其潜在机制。结果显示，KAT2A在NSCLC中的表达明显升高，且与预后不良有关。KAT2A敲低抑制NSCLC细胞生长和糖酵解。机制上，KAT2A敲低可降低转化生长因子β受体2 （TGFβR2）在赖氨酸493位点的琥珀酰化，导致TGFβR2表达降低。该位点的突变减弱了TGFβR2过表达诱导的致癌和糖酵解作用。此外，体内实验表明，KAT2A敲低可显著抑制肿瘤生长。我们的研究结果表明，KAT2A通过调节TGFβR2的琥珀酰化，在非小细胞肺癌中发挥致癌驱动作用，强调了其作为治疗靶点的潜力。

{"title":"KAT2A accelerates lung cancer progression through succinylation of TGFβR2","authors":"Mingqiang Shen , Qingqing Sun , Jinjiao Zhang , Tengfang Zhang , Lei Zhang","doi":"10.1016/j.tice.2025.103254","DOIUrl":"10.1016/j.tice.2025.103254","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is one of the leading causes of cancer-related mortality worldwide. Succinylation has been implicated in the pathogenesis of NSCLC at the molecular level. The succinyltransferase lysine acetyltransferase 2 A (KAT2A) exhibits oncogenic properties in diverse cancers; however, its role in NSCLC development remains unclear. This study employed bioinformatics techniques, clinical specimens, and NSCLC cell lines to analyze KAT2A expression. Cell malignancy was assessed using the cell counting kit-8 (CCK-8) and colony-formation assays. Glycolytic activity was evaluated by measuring glucose uptake, lactate production, extracellular acidification rate, and oxygen consumption rate. The underlying mechanisms were explored using quantitative real-time polymerase chain reaction, immunoblotting, immunoprecipitation, immunofluorescence, and cycloheximide chase assays. The results showed that KAT2A expression was notably higher in NSCLC and was linked to poor prognosis. Knockdown of KAT2A suppressed NSCLC cell growth and glycolysis. Mechanistically, KAT2A knockdown reduced the succinylation of transforming growth factor beta receptor 2 (TGFβR2) at lysine 493, leading to decreased expression of TGFβR2. A mutation at this site attenuated the oncogenic and glycolytic effects induced by TGFβR2 overexpression. Moreover, <em>in vivo</em> experiments demonstrated that KAT2A knockdown markedly inhibited tumor growth. Our findings suggest that KAT2A functions as an oncogenic driver in NSCLC by modulating the succinylation of TGFβR2, underscoring its potential as a therapeutic target.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103254"},"PeriodicalIF":2.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Nuclear receptor ERRγ acts as a key transcriptional regulator of hepatic LCN2 expression in CCl4-induced acute liver injury 在ccl4诱导的急性肝损伤中，核受体ERRγ是肝脏LCN2表达的关键转录调节因子

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-27 DOI: 10.1016/j.tice.2025.103250

Byungyoon Choi , Yoon Seok Jung , Woo-Ram Park , Yong-Hoon Kim , Chul-Ho Lee , Hueng-Sik Choi , Don-Kyu Kim

Estrogen-related receptor γ (ERRγ) is a nuclear receptor and transcription factor that plays an important role in liver metabolism by regulating the transcription of genes involved in inflammation, alcohol metabolism, and iron metabolism. Lipocalin 2 (LCN2) is a secreted protein that regulates inflammation, immune response, and iron homeostasis and is involved in liver injury. However, the transcriptional regulation of LCN2 in the liver remains largely unknown. Here, we showed that ERRγ is a critical transcriptional regulator of the hepatic LCN2 gene in carbon tetrachloride (CCl₄)-induced acute liver injury. CCl₄ treatment significantly increased hepatic ERRγ and LCN2 gene expression by inducing interleukin-6 (IL-6) expression in mice. Interestingly, ERRγ overexpression increased LCN2 gene expression and secretion in the livers of mice. Conversely, mice with the liver-specific knockout of ERRγ (ERRγ-LKO) exhibited significantly decreased CCl₄-induced LCN2 gene expression in the liver. Moreover, IL-6 treatment increased LCN2 expression and secretion in the livers of wild-type mice, which was significantly attenuated in ERRγ-LKO mice. Furthermore, deletion and mutation analyses revealed that ERRγ directly binds to ERR-response elements in the LCN2 promoter, modulating LCN2 gene transcription; these data were confirmed by a chromatin immunoprecipitation assay. Finally, administering GSK5182, an inverse agonist of ERRγ, significantly reduced the CCl₄-induced levels of LCN2 mRNA and protein in the liver. These findings suggest that ERRγ is a previously unrecognized transcriptional regulator of LCN2 in CCl₄-mediated acute liver injury.

雌激素相关受体γ (Estrogen-related receptor γ, ERRγ)是一种核受体和转录因子，通过调节炎症、酒精代谢和铁代谢相关基因的转录，在肝脏代谢中发挥重要作用。脂载蛋白2 （Lipocalin 2, LCN2）是一种调节炎症、免疫反应和铁稳态的分泌蛋白，参与肝损伤。然而，LCN2在肝脏中的转录调控在很大程度上仍然未知。在这里，我们发现ERRγ是四氯化碳（CCl4）诱导的急性肝损伤中肝脏LCN2基因的关键转录调节因子。CCl4通过诱导白细胞介素-6 （IL-6）表达，显著提高小鼠肝脏ERRγ和LCN2基因表达。有趣的是，ERRγ过表达增加了小鼠肝脏中LCN2基因的表达和分泌。相反，肝脏特异性敲除ERRγ (ERRγ- lko)的小鼠肝脏中ccl4诱导的LCN2基因表达显著降低。此外，IL-6处理增加了野生型小鼠肝脏中LCN2的表达和分泌，而在erγ - lko小鼠中则明显减弱。此外，缺失和突变分析表明，ERRγ直接结合LCN2启动子中的err应答元件，调节LCN2基因转录；这些数据通过染色质免疫沉淀试验得到证实。最后，给药ERRγ的逆激动剂GSK5182显著降低了ccl4诱导的肝脏中LCN2 mRNA和蛋白的水平。这些发现表明，在ccl4介导的急性肝损伤中，ERRγ是LCN2先前未被识别的转录调节因子。

{"title":"Nuclear receptor ERRγ acts as a key transcriptional regulator of hepatic LCN2 expression in CCl4-induced acute liver injury","authors":"Byungyoon Choi , Yoon Seok Jung , Woo-Ram Park , Yong-Hoon Kim , Chul-Ho Lee , Hueng-Sik Choi , Don-Kyu Kim","doi":"10.1016/j.tice.2025.103250","DOIUrl":"10.1016/j.tice.2025.103250","url":null,"abstract":"<div><div>Estrogen-related receptor γ (ERRγ) is a nuclear receptor and transcription factor that plays an important role in liver metabolism by regulating the transcription of genes involved in inflammation, alcohol metabolism, and iron metabolism. Lipocalin 2 (LCN2) is a secreted protein that regulates inflammation, immune response, and iron homeostasis and is involved in liver injury. However, the transcriptional regulation of LCN2 in the liver remains largely unknown. Here, we showed that ERRγ is a critical transcriptional regulator of the hepatic <em>LCN2</em> gene in carbon tetrachloride (CCl<sub>4</sub>)-induced acute liver injury. CCl<sub>4</sub> treatment significantly increased hepatic <em>ERRγ</em> and <em>LCN2</em> gene expression by inducing interleukin-6 (IL-6) expression in mice. Interestingly, ERRγ overexpression increased <em>LCN2</em> gene expression and secretion in the livers of mice. Conversely, mice with the liver-specific knockout of ERRγ (ERRγ-LKO) exhibited significantly decreased CCl<sub>4</sub>-induced <em>LCN2</em> gene expression in the liver. Moreover, IL-6 treatment increased <em>LCN2</em> expression and secretion in the livers of wild-type mice, which was significantly attenuated in ERRγ-LKO mice. Furthermore, deletion and mutation analyses revealed that ERRγ directly binds to ERR-response elements in the <em>LCN2</em> promoter, modulating <em>LCN2</em> gene transcription; these data were confirmed by a chromatin immunoprecipitation assay. Finally, administering GSK5182, an inverse agonist of ERRγ, significantly reduced the CCl<sub>4</sub>-induced levels of LCN2 mRNA and protein in the liver. These findings suggest that ERRγ is a previously unrecognized transcriptional regulator of <em>LCN2</em> in CCl<sub>4</sub>-mediated acute liver injury.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103250"},"PeriodicalIF":2.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Innovative approaches for microfluidics techniques in tissue engineering and revolutionizing sports medicine: Enhancing athletic performance and recovery using finite element and statistical analysis 微流体技术在组织工程和革命性运动医学中的创新方法：利用有限元和统计分析提高运动表现和恢复。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-27 DOI: 10.1016/j.tice.2025.103251

Yu Ruida , Rong Siyu , Qi Yufei , A. Shahbaz , Sh. Baghaei

Microfluidics is the science and technology of systems that process tiny amounts of fluid using channels with dimensions ranging from 10 to 100 micrometers. This field addresses the behavior, precise control, and maintenance of fluids geometrically constrained to small scales, typically below the millimeter range. Microfluidic systems collaborate with various disciplines to design diverse applications. Microfluidics is inherently interdisciplinary, encompassing fields such as medicine, physics, biology, materials science, mechanical engineering, and electronics. Key drivers of microfluidics include molecular analysis, biosafety, molecular biology, and microelectronics. Microchannels can be fabricated on various substrates, including glass, polymers, plastics, ceramics, and metals. Fluid behavior at the micro-scale differs from the macro-scale due to low thermal mass and high surface-to-volume ratios, leading to rapid heat transfer and precise temperature control. Significant advancements in microfluidics were limited until recent decades, when researchers conducted extensive studies to develop new microfluidic components. This work employs Finite Element Analysis (FEA) to model fluid dynamics in key microfluidic systems. Complementarily, a statistical analysis of design parameters quantifies a critical performance trade-off, providing a data-driven framework for optimizing devices towards either high-throughput efficiency or high-precision measurement for targeted applications in sports medicine. The Lab-on-a-Chip (LOC) paradigm represents an integrative framework of cohesive unit operations engineered to provide precise, expedient, and efficient control within biological and chemical domains. Microfluidic technology holds immense potential to revolutionize healthcare, from diagnostics and therapeutics to regenerative and sport medicine. As a result, microfluidic technologies are set to revolutionize sports medicine, fostering a new era of tailored health management and sport performance optimization.

微流体学是一门科学和系统技术，它使用尺寸范围从10到100微米的通道处理微量流体。该领域解决了流体的行为、精确控制和维护问题，这些流体的几何尺寸通常小于毫米。微流控系统与不同学科合作设计不同的应用。微流体学本质上是跨学科的，涵盖了医学、物理学、生物学、材料科学、机械工程和电子学等领域。微流控的主要驱动力包括分子分析、生物安全、分子生物学和微电子学。微通道可以在各种基板上制造，包括玻璃、聚合物、塑料、陶瓷和金属。微观尺度下的流体行为不同于宏观尺度，这是由于低热质量和高表面体积比，从而导致快速的传热和精确的温度控制。直到最近几十年，当研究人员进行了广泛的研究以开发新的微流控元件时，微流控的重大进展才受到限制。本工作采用有限元分析（FEA）来模拟关键微流体系统的流体动力学。此外，设计参数的统计分析量化了关键性能权衡，为优化设备提供了数据驱动的框架，以实现高通量效率或高精度测量，用于运动医学的目标应用。芯片实验室（LOC）范例代表了一个内聚单元操作的综合框架，旨在在生物和化学领域提供精确，方便和有效的控制。从诊断和治疗到再生和运动医学，微流控技术具有巨大的潜力，可以彻底改变医疗保健。因此，微流控技术将彻底改变运动医学，开创量身定制的健康管理和运动表现优化的新时代。

{"title":"Innovative approaches for microfluidics techniques in tissue engineering and revolutionizing sports medicine: Enhancing athletic performance and recovery using finite element and statistical analysis","authors":"Yu Ruida , Rong Siyu , Qi Yufei , A. Shahbaz , Sh. Baghaei","doi":"10.1016/j.tice.2025.103251","DOIUrl":"10.1016/j.tice.2025.103251","url":null,"abstract":"<div><div>Microfluidics is the science and technology of systems that process tiny amounts of fluid using channels with dimensions ranging from 10 to 100 micrometers. This field addresses the behavior, precise control, and maintenance of fluids geometrically constrained to small scales, typically below the millimeter range. Microfluidic systems collaborate with various disciplines to design diverse applications. Microfluidics is inherently interdisciplinary, encompassing fields such as medicine, physics, biology, materials science, mechanical engineering, and electronics. Key drivers of microfluidics include molecular analysis, biosafety, molecular biology, and microelectronics. Microchannels can be fabricated on various substrates, including glass, polymers, plastics, ceramics, and metals. Fluid behavior at the micro-scale differs from the macro-scale due to low thermal mass and high surface-to-volume ratios, leading to rapid heat transfer and precise temperature control. Significant advancements in microfluidics were limited until recent decades, when researchers conducted extensive studies to develop new microfluidic components. This work employs Finite Element Analysis (FEA) to model fluid dynamics in key microfluidic systems. Complementarily, a statistical analysis of design parameters quantifies a critical performance trade-off, providing a data-driven framework for optimizing devices towards either high-throughput efficiency or high-precision measurement for targeted applications in sports medicine. The Lab-on-a-Chip (LOC) paradigm represents an integrative framework of cohesive unit operations engineered to provide precise, expedient, and efficient control within biological and chemical domains. Microfluidic technology holds immense potential to revolutionize healthcare, from diagnostics and therapeutics to regenerative and sport medicine. As a result, microfluidic technologies are set to revolutionize sports medicine, fostering a new era of tailored health management and sport performance optimization.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103251"},"PeriodicalIF":2.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

PRMT1 promotes H2O2 induced cardiomyocytes cell via mediating arginine methylation of P53 PRMT1通过介导P53的精氨酸甲基化促进H2O2诱导的心肌细胞的形成。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-27 DOI: 10.1016/j.tice.2025.103253

Zhaojie Li , Jianqiang Zhao

Background

Abnormal methylation of protein arginine can cause dysfunction of cardiomyocytes, it is important to further elucidate the molecular mechanism.

Method

Candidate protein arginine methyltransferases (PRMTs) were selected using blood samples of myocardial infarction (MI) and control group. The isolated primary cardiomyocyte (PC) and H9C2 cells were treated with H₂O₂ to mimic MI in vitro and rats with myocardial ischemia-reperfusion (I/R) were established to mimic MI in vivo. The protein content of PRMT1 methylation product P53 was detected to reflect the PRMT1 activity.

Result

PRMT1 was aberrant upregulated in MI models. PRMT1 ablation suppressed cell apoptosis and inflammatory cytokine secretion to reverse the H₂O₂ function. The upregulation of PRMT1 accelerated the degradation of P53 protein through the arginine methylation. Inhibition of PRMT1 alleviated cardiac damage after I/R in rats.

Conclusion

PRMT1 promoted MI by mediating arginine methylation of P53. PRMT1 may be a promising therapeutic target for MI.

背景：蛋白精氨酸异常甲基化可引起心肌细胞功能障碍，进一步阐明其分子机制具有重要意义。方法：从心肌梗死（MI）患者和对照组的血液样本中选择候选蛋白精氨酸甲基转移酶（PRMTs）。将分离的原代心肌细胞（PC）和H9C2细胞用H2O2处理体外模拟心肌梗死，并建立心肌缺血再灌注（I/R）大鼠体内模拟心肌梗死。检测PRMT1甲基化产物P53蛋白含量，反映PRMT1活性。结果：心肌梗死模型中PRMT1异常上调。消融PRMT1抑制细胞凋亡和炎性细胞因子分泌，逆转H2O2功能。PRMT1的上调通过精氨酸甲基化加速了P53蛋白的降解。抑制PRMT1可减轻大鼠I/R后心脏损伤。结论：PRMT1通过介导P53精氨酸甲基化促进心肌梗死。PRMT1可能是心肌梗死的一个有希望的治疗靶点。

{"title":"PRMT1 promotes H2O2 induced cardiomyocytes cell via mediating arginine methylation of P53","authors":"Zhaojie Li , Jianqiang Zhao","doi":"10.1016/j.tice.2025.103253","DOIUrl":"10.1016/j.tice.2025.103253","url":null,"abstract":"<div><h3>Background</h3><div>Abnormal methylation of protein arginine can cause dysfunction of cardiomyocytes, it is important to further elucidate the molecular mechanism.</div></div><div><h3>Method</h3><div>Candidate protein arginine methyltransferases (PRMTs) were selected using blood samples of myocardial infarction (MI) and control group. The isolated primary cardiomyocyte (PC) and H9C2 cells were treated with H<sub>2</sub>O<sub>2</sub> to mimic MI <em>in vitro</em> and rats with myocardial ischemia-reperfusion (I/R) were established to mimic MI <em>in vivo.</em> The protein content of PRMT1 methylation product P53 was detected to reflect the PRMT1 activity.</div></div><div><h3>Result</h3><div>PRMT1 was aberrant upregulated in MI models. PRMT1 ablation suppressed cell apoptosis and inflammatory cytokine secretion to reverse the H<sub>2</sub>O<sub>2</sub> function. The upregulation of PRMT1 accelerated the degradation of P53 protein through the arginine methylation. Inhibition of PRMT1 alleviated cardiac damage after I/R in rats.</div></div><div><h3>Conclusion</h3><div>PRMT1 promoted MI by mediating arginine methylation of P53. PRMT1 may be a promising therapeutic target for MI.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103253"},"PeriodicalIF":2.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Gut-derived Helicobacter rodentium aggravates Tfh/Tfr imbalance and neuroinflammation via PI3K/AKT activation in anti-NMDAR encephalitis mice 在抗nmdar脑炎小鼠中，肠道源性螺杆菌通过激活PI3K/AKT加重Tfh/Tfr失衡和神经炎症

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-25 DOI: 10.1016/j.tice.2025.103242

Yanfei Yang, Lili Yang, Yabin Li, Yanfen Wang

Background

The gut microbiota is essential for the bidirectional communication between the gut and the brain. However, its specific role and underlying mechanisms in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis remain largely unclear.

Methods

An anti-NMDAR encephalitis model was induced by GluN1 peptide immunization, and brain histopathology was assessed by hematoxylin-eosin staining. Behavioral performance was assessed through the Y-maze and open field tests. Flow cytometry was employed to quantify T follicular helper (Tfh) and T follicular regulatory (Tfr) cell populations. Enzyme-linked immunosorbent assay and western blot were used to assess inflammatory cytokines and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway-related protein levels, respectively. 16S rRNA sequencing and Helicobacter rodentium gavage (1.5 mL, 1 ×10 ¹¹ CFU/mL) were used to assess microbiota composition and bacterial function.

Results

16S rRNA sequencing revealed a trend toward reduced gut microbial diversity in anti-NMDAR encephalitis mice. Helicobacter rodentium colonization further exacerbated behavioral deficits and inflammatory cell infiltration in the cerebral cortex. This was accompanied by a marked increase in tumor necrosis factor alpha (TNF-α) and interleukin (IL)-21 levels and a reduction in IL-10 concentrations in both cerebrospinal fluid and serum. Moreover, the Tfh/Tfr cell ratio was further elevated following Helicobacter rodentium exposure. Targeted suppression of the PI3K/AKT pathway with LY294002 significantly restored Tfh/Tfr balance and alleviated neurobehavioral impairments and cortical inflammation.

Conclusion

Helicobacter rodentium exacerbates anti-NMDAR encephalitis by inducing PI3K/AKT-mediated Tfh/Tfr imbalance, highlighting a potential therapeutic target in autoimmune encephalitis.

肠道微生物群对于肠道和大脑之间的双向交流至关重要。然而，其在抗n -甲基- d -天冬氨酸受体（NMDAR）脑炎中的具体作用和潜在机制仍不清楚。方法采用GluN1肽免疫诱导抗nmdar脑炎模型，苏木精-伊红染色观察脑组织病理学变化。通过y形迷宫和野外测试评估行为表现。流式细胞术定量T滤泡辅助（Tfh）和T滤泡调节（Tfr）细胞群。采用酶联免疫吸附法和western blot分别检测炎症因子和磷酸肌苷3-激酶/蛋白激酶B （PI3K/AKT）通路相关蛋白水平。采用16S rRNA测序和螺杆菌灌胃（1.5 mL, 1 ×10 ¹¹CFU/mL）评估菌群组成和细菌功能。结果16s rRNA测序显示抗nmdar脑炎小鼠肠道微生物多样性降低的趋势。啮齿螺杆菌的定植进一步加剧了行为缺陷和大脑皮层的炎症细胞浸润。脑脊液和血清中肿瘤坏死因子α (TNF-α)和白细胞介素(IL)-21水平显著升高，IL-10浓度降低。此外，幽门螺杆菌暴露后，Tfh/Tfr细胞比值进一步升高。LY294002靶向抑制PI3K/AKT通路可显著恢复Tfh/Tfr平衡，减轻神经行为障碍和皮质炎症。结论啮齿螺杆菌通过诱导PI3K/ akt介导的Tfh/Tfr失衡加重抗nmdar脑炎，提示自身免疫性脑炎的潜在治疗靶点。

{"title":"Gut-derived Helicobacter rodentium aggravates Tfh/Tfr imbalance and neuroinflammation via PI3K/AKT activation in anti-NMDAR encephalitis mice","authors":"Yanfei Yang, Lili Yang, Yabin Li, Yanfen Wang","doi":"10.1016/j.tice.2025.103242","DOIUrl":"10.1016/j.tice.2025.103242","url":null,"abstract":"<div><h3>Background</h3><div>The gut microbiota is essential for the bidirectional communication between the gut and the brain. However, its specific role and underlying mechanisms in anti-N-methyl-<span>D</span>-aspartate receptor (NMDAR) encephalitis remain largely unclear.</div></div><div><h3>Methods</h3><div>An anti-NMDAR encephalitis model was induced by GluN1 peptide immunization, and brain histopathology was assessed by hematoxylin-eosin staining. Behavioral performance was assessed through the Y-maze and open field tests. Flow cytometry was employed to quantify T follicular helper (Tfh) and T follicular regulatory (Tfr) cell populations. Enzyme-linked immunosorbent assay and western blot were used to assess inflammatory cytokines and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway-related protein levels, respectively. 16S rRNA sequencing and <em>Helicobacter rodentium</em> gavage (1.5 mL, 1 ×10 ¹¹ CFU/mL) were used to assess microbiota composition and bacterial function.</div></div><div><h3>Results</h3><div>16S rRNA sequencing revealed a trend toward reduced gut microbial diversity in anti-NMDAR encephalitis mice. <em>Helicobacter rodentium</em> colonization further exacerbated behavioral deficits and inflammatory cell infiltration in the cerebral cortex. This was accompanied by a marked increase in tumor necrosis factor alpha (TNF-α) and interleukin (IL)-21 levels and a reduction in IL-10 concentrations in both cerebrospinal fluid and serum. Moreover, the Tfh/Tfr cell ratio was further elevated following <em>Helicobacter rodentium</em> exposure. Targeted suppression of the PI3K/AKT pathway with LY294002 significantly restored Tfh/Tfr balance and alleviated neurobehavioral impairments and cortical inflammation.</div></div><div><h3>Conclusion</h3><div><em>Helicobacter rodentium</em> exacerbates anti-NMDAR encephalitis by inducing PI3K/AKT-mediated Tfh/Tfr imbalance, highlighting a potential therapeutic target in autoimmune encephalitis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103242"},"PeriodicalIF":2.5,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

RBM15-mediated m6A modification upregulates KDM2A to promote ferroptosis in osteoarthritis cells rbm15介导的m6A修饰上调KDM2A，促进骨关节炎细胞铁凋亡。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-24 DOI: 10.1016/j.tice.2025.103248

Changdong Fan , Jing Ma , Fengliang Fan , Rongbing Yi , Wenbo Wang

Background and aims

Ferroptosis has been acknowledged to be involved in the progression of osteoarthritis (OA), contributing to chondrocyte damage and articular cartilage degradation. This investigation seeks to explain the mechanism of RBM15 in ferroptosis of OA cell models.

Methods

OA cell model was established using IL-1β-induced chondrocytes. After silencing RBM15 expression, TNF-α and IL-6 were detected, cell viability was measured, LDH, Fe²⁺, ROS, MDA, and GSH were assessed, and ACSL4 and SLC7A11 expression was quantified. RT-qPCR and Western blot were employed to detect the expression of RBM15, KDM2A, and HOXA2. The m6A content in cells was assayed using a kit. RIP assay was utilized to analyze m6A modification on KDM2A. Dual-luciferase assay was employed to validate RBM15-mediated m6A modification on KDM2A. RT-qPCR was applied to examine KDM2A mRNA stability. ChIP was employed to assess the enrichment of KDM2A and H3K36me2 at the HOXA2 promoter. Combined experiments were designed to elucidate the role of KDM2A and HOXA2 in ferroptosis of OA cell models.

Results

RBM15 and KDM2A were upregulated, while HOXA2 was reduced in IL-1β-stimulated chondrocytes. RBM15 downregulation enhanced chondrocyte viability and mitigated ferroptosis. RBM15-mediated m6A modification upregulated KDM2A, suppressed H3K36me2 enrichment at the HOXA2 promoter, and inhibited HOXA2 expression. Overexpression of KDM2A and downregulation of HOXA2 could partially counteract the suppressive effect of RBM15 silencing on chondrocyte ferroptosis.

Conclusion

RBM15-mediated m6A modification upregulates KDM2A to inhibit HOXA2 expression by reducing H3K36me2 enrichment, thus promoting IL-1β-induced chondrocyte ferroptosis.

背景和目的：上睑下垂已被认为与骨关节炎（OA）的进展有关，有助于软骨细胞损伤和关节软骨降解。本研究旨在解释RBM15在OA细胞模型铁下垂中的作用机制。方法：采用il -1β诱导软骨细胞建立OA细胞模型。沉默RBM15表达后，检测TNF-α和IL-6，测定细胞活力，检测LDH、Fe 2 +、ROS、MDA和GSH，量化ACSL4和SLC7A11的表达。采用RT-qPCR和Western blot检测RBM15、KDM2A、HOXA2的表达。用试剂盒检测细胞中m6A的含量。RIP法分析m6A对KDM2A的修饰。双荧光素酶法验证了rbm15介导的m6A在KDM2A上的修饰。采用RT-qPCR检测KDM2A mRNA的稳定性。利用ChIP评估KDM2A和H3K36me2在HOXA2启动子上的富集情况。我们设计了联合实验来阐明KDM2A和HOXA2在OA细胞模型铁凋亡中的作用。结果：在il -1β刺激的软骨细胞中，RBM15和KDM2A上调，HOXA2降低。RBM15下调可增强软骨细胞活力，减轻铁下垂。rbm15介导的m6A修饰上调KDM2A，抑制H3K36me2在HOXA2启动子处的富集，抑制HOXA2的表达。KDM2A的过表达和HOXA2的下调可以部分抵消RBM15沉默对软骨细胞铁下垂的抑制作用。结论：rbm15介导的m6A修饰上调KDM2A，通过降低H3K36me2的富集抑制HOXA2的表达，从而促进il -1β诱导的软骨细胞铁凋亡。

{"title":"RBM15-mediated m6A modification upregulates KDM2A to promote ferroptosis in osteoarthritis cells","authors":"Changdong Fan , Jing Ma , Fengliang Fan , Rongbing Yi , Wenbo Wang","doi":"10.1016/j.tice.2025.103248","DOIUrl":"10.1016/j.tice.2025.103248","url":null,"abstract":"<div><h3>Background and aims</h3><div>Ferroptosis has been acknowledged to be involved in the progression of osteoarthritis (OA), contributing to chondrocyte damage and articular cartilage degradation. This investigation seeks to explain the mechanism of RBM15 in ferroptosis of OA cell models.</div></div><div><h3>Methods</h3><div>OA cell model was established using IL-1β-induced chondrocytes. After silencing RBM15 expression, TNF-α and IL-6 were detected, cell viability was measured, LDH, Fe²⁺, ROS, MDA, and GSH were assessed, and ACSL4 and SLC7A11 expression was quantified. RT-qPCR and Western blot were employed to detect the expression of RBM15, KDM2A, and HOXA2. The m6A content in cells was assayed using a kit. RIP assay was utilized to analyze m6A modification on KDM2A. Dual-luciferase assay was employed to validate RBM15-mediated m6A modification on KDM2A. RT-qPCR was applied to examine KDM2A mRNA stability. ChIP was employed to assess the enrichment of KDM2A and H3K36me2 at the HOXA2 promoter. Combined experiments were designed to elucidate the role of KDM2A and HOXA2 in ferroptosis of OA cell models.</div></div><div><h3>Results</h3><div>RBM15 and KDM2A were upregulated, while HOXA2 was reduced in IL-1β-stimulated chondrocytes. RBM15 downregulation enhanced chondrocyte viability and mitigated ferroptosis. RBM15-mediated m6A modification upregulated KDM2A, suppressed H3K36me2 enrichment at the HOXA2 promoter, and inhibited HOXA2 expression. Overexpression of KDM2A and downregulation of HOXA2 could partially counteract the suppressive effect of RBM15 silencing on chondrocyte ferroptosis.</div></div><div><h3>Conclusion</h3><div>RBM15-mediated m6A modification upregulates KDM2A to inhibit HOXA2 expression by reducing H3K36me2 enrichment, thus promoting IL-1β-induced chondrocyte ferroptosis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103248"},"PeriodicalIF":2.5,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Analysis of WNT5A as a key regulator of intramuscular fat deposition in muscle-adipocyte co-cultures 分析WNT5A作为肌肉-脂肪细胞共培养中肌内脂肪沉积的关键调节因子

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-11-24 DOI: 10.1016/j.tice.2025.103245

Hongfang Gong , Yaping Song , Dongmei Yang , Chao Jiang , Ruopu Jiao , Yilun Ma , Sayed Haidar Abbas Raza , Jiupan Zhang , Dawei Wei

The coordinated development of skeletal muscle and intramuscular adipose tissue in animals essentially determines meat yield and quality, a process co-regulated by multiple genes. Using a co-culture model of bovine skeletal muscle cells (SMCs) and intramuscular adipocytes (IMAs), integrated with transcriptomic sequencing and bioinformatic analyses, key candidate genes coregulating muscle development and fat deposition were identified. Three potential coregulators—WNT5A, APOE, and BDKRB2—were selected. Protein-protein interaction (PPI) network analysis, along with tissue and cellular expression profiling, indicates that WNT5A potentially interacts with key protein markers of adipogenesis and myogenesis. Furthermore, it is highly expressed in both adipose and muscle tissues. Pathway enrichment analysis revealed significant enrichment of WNT5A in the Wnt signaling pathway. These findings suggest that WNT5A plays a dual regulatory role in the development of both skeletal muscle and intramuscular fat (IMF). This finding lays a solid theoretical foundation for deciphering the molecular mechanisms of muscle-fat deposition in beef cattle and for improving meat quality.

动物骨骼肌和肌内脂肪组织的协调发育从本质上决定了肉的产量和品质，这一过程由多个基因共同调控。利用牛骨骼肌细胞（SMCs）和肌内脂肪细胞（IMAs）共培养模型，结合转录组测序和生物信息学分析，确定了协同调节肌肉发育和脂肪沉积的关键候选基因。三个潜在的协同调节因子- wnt5a， APOE和bdkrb2 -被选中。蛋白-蛋白相互作用（PPI）网络分析以及组织和细胞表达谱表明，WNT5A可能与脂肪形成和肌肉形成的关键蛋白标志物相互作用。此外，它在脂肪和肌肉组织中都高度表达。通路富集分析显示Wnt信号通路中WNT5A显著富集。这些发现表明WNT5A在骨骼肌和肌内脂肪（IMF）的发育中起双重调节作用。这一发现为破解肉牛肌肉脂肪沉积的分子机制，提高肉质品质奠定了坚实的理论基础。

{"title":"Analysis of WNT5A as a key regulator of intramuscular fat deposition in muscle-adipocyte co-cultures","authors":"Hongfang Gong , Yaping Song , Dongmei Yang , Chao Jiang , Ruopu Jiao , Yilun Ma , Sayed Haidar Abbas Raza , Jiupan Zhang , Dawei Wei","doi":"10.1016/j.tice.2025.103245","DOIUrl":"10.1016/j.tice.2025.103245","url":null,"abstract":"<div><div>The coordinated development of skeletal muscle and intramuscular adipose tissue in animals essentially determines meat yield and quality, a process co-regulated by multiple genes. Using a co-culture model of bovine skeletal muscle cells (SMCs) and intramuscular adipocytes (IMAs), integrated with transcriptomic sequencing and bioinformatic analyses, key candidate genes coregulating muscle development and fat deposition were identified. Three potential coregulators—<em>WNT5A</em>, <em>APOE</em>, and <em>BDKRB2</em>—were selected. Protein-protein interaction (PPI) network analysis, along with tissue and cellular expression profiling, indicates that WNT5A potentially interacts with key protein markers of adipogenesis and myogenesis. Furthermore, it is highly expressed in both adipose and muscle tissues. Pathway enrichment analysis revealed significant enrichment of <em>WNT5A</em> in the Wnt signaling pathway. These findings suggest that <em>WNT5A</em> plays a dual regulatory role in the development of both skeletal muscle and intramuscular fat (IMF). This finding lays a solid theoretical foundation for deciphering the molecular mechanisms of muscle-fat deposition in beef cattle and for improving meat quality.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103245"},"PeriodicalIF":2.5,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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