首页 > 最新文献

Inflammation and Regeneration最新文献

英文 中文
Th22 is the effector cell of thymosin β15-induced hair regeneration in mice Th22 是胸腺肽 β15 诱导小鼠毛发再生的效应细胞
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-01-08 DOI: 10.1186/s41232-023-00316-z
Nana Tao, Yuyuan Ying, Xie Xu, Qingru Sun, Yaoying Shu, Shiyu Hu, Zhaohuan Lou, Jianli Gao
{"title":"Th22 is the effector cell of thymosin β15-induced hair regeneration in mice","authors":"Nana Tao, Yuyuan Ying, Xie Xu, Qingru Sun, Yaoying Shu, Shiyu Hu, Zhaohuan Lou, Jianli Gao","doi":"10.1186/s41232-023-00316-z","DOIUrl":"https://doi.org/10.1186/s41232-023-00316-z","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"18 3","pages":"1-13"},"PeriodicalIF":8.1,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139379897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The gut-liver axis in hepatobiliary diseases 肝胆疾病中的肠肝轴
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-01-08 DOI: 10.1186/s41232-023-00315-0
Masataka Ichikawa, Haruka Okada, N. Nakamoto, N. Taniki, Po-sung Chu, Takanori Kanai
{"title":"The gut-liver axis in hepatobiliary diseases","authors":"Masataka Ichikawa, Haruka Okada, N. Nakamoto, N. Taniki, Po-sung Chu, Takanori Kanai","doi":"10.1186/s41232-023-00315-0","DOIUrl":"https://doi.org/10.1186/s41232-023-00315-0","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"36 3","pages":"1-16"},"PeriodicalIF":8.1,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139380071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling dynamic interactions: in vivo imaging chronicles inflammation and regeneration in living organisms 揭示动态相互作用:活体成像记录生物体的炎症和再生过程
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 10.1186/s41232-023-00312-3
K. Kabashima
{"title":"Unveiling dynamic interactions: in vivo imaging chronicles inflammation and regeneration in living organisms","authors":"K. Kabashima","doi":"10.1186/s41232-023-00312-3","DOIUrl":"https://doi.org/10.1186/s41232-023-00312-3","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"116 9","pages":""},"PeriodicalIF":8.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138608104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inter-organ communication involved in metabolic regulation at the whole-body level 全身代谢调节所涉及的器官间交流
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 10.1186/s41232-023-00306-1
Hideki Katagiri
{"title":"Inter-organ communication involved in metabolic regulation at the whole-body level","authors":"Hideki Katagiri","doi":"10.1186/s41232-023-00306-1","DOIUrl":"https://doi.org/10.1186/s41232-023-00306-1","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" October","pages":""},"PeriodicalIF":8.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138611130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A disease-specific iPS cell resource for studying rare and intractable diseases. 一种用于研究罕见和难治性疾病的疾病特异性iPS细胞资源。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-09-08 DOI: 10.1186/s41232-023-00294-2
Megumu K Saito, Mitsujiro Osawa, Nao Tsuchida, Kotaro Shiraishi, Akira Niwa, Knut Woltjen, Isao Asaka, Katsuhisa Ogata, Suminobu Ito, Shuzo Kobayashi, Shinya Yamanaka

Background: Disease-specific induced pluripotent stem cells (iPSCs) are useful tools for pathological analysis and diagnosis of rare diseases. Given the limited available resources, banking such disease-derived iPSCs and promoting their widespread use would be a promising approach for untangling the mysteries of rare diseases. Herein, we comprehensively established iPSCs from patients with designated intractable diseases in Japan and evaluated their properties to enrich rare disease iPSC resources.

Methods: Patients with designated intractable diseases were recruited for the study and blood samples were collected after written informed consent was obtained from the patients or their guardians. From the obtained samples, iPSCs were established using the episomal method. The established iPSCs were deposited in a cell bank.

Results: We established 1,532 iPSC clones from 259 patients with 139 designated intractable diseases. The efficiency of iPSC establishment did not vary based on age and sex. Most iPSC clones originated from non-T and non-B hematopoietic cells. All iPSC clones expressed key transcription factors, OCT3/4 (range 0.27-1.51; mean 0.79) and NANOG (range 0.15-3.03; mean 1.00), relative to the reference 201B7 iPSC clone.

Conclusions: These newly established iPSCs are readily available to the researchers and can prove to be a useful resource for research on rare intractable diseases.

背景:疾病特异性诱导多能干细胞(iPSCs)是罕见病病理分析和诊断的有用工具。鉴于现有资源有限,储存这种源自疾病的多能干细胞并促进其广泛使用将是解开罕见疾病之谜的一种有希望的方法。在此,我们全面构建了来自日本指定顽固性疾病患者的iPSC,并评估了它们的性质,以丰富罕见病iPSC资源。方法:招募指定顽固性疾病患者,经患者或其监护人书面知情同意后采集血样。从获得的样品中,使用episomal方法建立iPSCs。建立的iPSCs储存在细胞库中。结果:我们从139种指定顽固性疾病的259例患者中建立了1532个iPSC克隆。iPSC的建立效率不受年龄和性别的影响。大多数iPSC克隆来源于非t和非b造血细胞。所有iPSC克隆均表达关键转录因子OCT3/4(范围0.27-1.51;平均0.79)和NANOG(范围0.15-3.03;平均1.00),相对于参考201B7 iPSC克隆。结论:这些新建立的多能干细胞对研究人员来说是很容易获得的,可以证明是罕见难治性疾病研究的有用资源。
{"title":"A disease-specific iPS cell resource for studying rare and intractable diseases.","authors":"Megumu K Saito, Mitsujiro Osawa, Nao Tsuchida, Kotaro Shiraishi, Akira Niwa, Knut Woltjen, Isao Asaka, Katsuhisa Ogata, Suminobu Ito, Shuzo Kobayashi, Shinya Yamanaka","doi":"10.1186/s41232-023-00294-2","DOIUrl":"10.1186/s41232-023-00294-2","url":null,"abstract":"<p><strong>Background: </strong>Disease-specific induced pluripotent stem cells (iPSCs) are useful tools for pathological analysis and diagnosis of rare diseases. Given the limited available resources, banking such disease-derived iPSCs and promoting their widespread use would be a promising approach for untangling the mysteries of rare diseases. Herein, we comprehensively established iPSCs from patients with designated intractable diseases in Japan and evaluated their properties to enrich rare disease iPSC resources.</p><p><strong>Methods: </strong>Patients with designated intractable diseases were recruited for the study and blood samples were collected after written informed consent was obtained from the patients or their guardians. From the obtained samples, iPSCs were established using the episomal method. The established iPSCs were deposited in a cell bank.</p><p><strong>Results: </strong>We established 1,532 iPSC clones from 259 patients with 139 designated intractable diseases. The efficiency of iPSC establishment did not vary based on age and sex. Most iPSC clones originated from non-T and non-B hematopoietic cells. All iPSC clones expressed key transcription factors, OCT3/4 (range 0.27-1.51; mean 0.79) and NANOG (range 0.15-3.03; mean 1.00), relative to the reference 201B7 iPSC clone.</p><p><strong>Conclusions: </strong>These newly established iPSCs are readily available to the researchers and can prove to be a useful resource for research on rare intractable diseases.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"43 1","pages":"43"},"PeriodicalIF":8.1,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10485998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10549517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Jdp2 is a spatiotemporal transcriptional activator of the AhR via the Nrf2 gene battery. jp2是通过Nrf2基因电池激活AhR的时空转录激活因子。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-08-18 DOI: 10.1186/s41232-023-00290-6
Kenly Wuputra, Ming-Ho Tsai, Kohsuke Kato, Chia-Chen Ku, Jia-Bin Pan, Ya-Han Yang, Shigeo Saito, Chun-Chieh Wu, Ying-Chu Lin, Kuang-Hung Cheng, Kung-Kai Kuo, Michiya Noguchi, Yukio Nakamura, Tohru Yoshioka, Deng-Chyang Wu, Chang-Shen Lin, Kazunari K Yokoyama

Background: Crosstalk between the aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is called the "AhR-Nrf2 gene battery", which works synergistically in detoxification to support cell survival. Nrf2-dependent phase II gene promoters are controlled by coordinated recruitment of the AhR to adjacent dioxin responsive element (DRE) and Nrf2 recruitment to the antioxidative response element (ARE). The molecular interaction between AhR and Nrf2 members, and the regulation of each target, including phase I and II gene complexes, and their mediators are poorly understood.

Methods: Knockdown and forced expression of AhR-Nrf2 battery members were used to examine the molecular interactions between the AhR-Nrf2 axis and AhR promoter activation. Sequential immunoprecipitation, chromatin immunoprecipitation, and histology were used to identify each protein complex recruited to their respective cis-elements in the AhR promoter. Actin fiber distribution, cell spreading, and invasion were examined to identify functional differences in the AhR-Jdp2 axis between wild-type and Jdp2 knockout cells. The possible tumorigenic role of Jdp2 in the AhR-Nrf2 axis was examined in mutant Kras-Trp53-driven pancreatic tumors.

Results: Crosstalk between AhR and Nrf2 was evident at the transcriptional level. The AhR promoter was activated by phase I ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the AhR-Jdp2-Nrf2 axis in a time- and spatial transcription-dependent manner. Jdp2 was a bifunctional activator of DRE- and ARE-mediated transcription in response to TCDD. After TCDD exposure, Jdp2 activated the AhR promoter at the DRE and then moved to the ARE where it activated the promoter to increase reactive oxygen species (ROS)-mediated functions such as cell spreading and invasion in normal cells, and cancer regression in mutant Kras-Trp53-driven pancreatic tumor cells.

Conclusions: Jdp2 plays a critical role in AhR promoter activation through the AhR-Jdp2-Nrf2 axis in a spatiotemporal manner. The AhR functions to maintain ROS balance and cell spreading, invasion, and cancer regression in a mouse model of mutant Kras-Trp53 pancreatic cancer. These findings provide new insights into the roles of Jdp2 in the homeostatic regulation of oxidative stress and in the antioxidation response in detoxification, inflammation, and cancer progression.

背景:芳烃受体(AhR)和核因子(红细胞衍生2)样2 (Nrf2)信号传导之间的串扰被称为“AhR-Nrf2基因电池”,它们协同作用于解毒以支持细胞存活。Nrf2依赖的II期基因启动子通过AhR对相邻二恶英反应元件(DRE)和Nrf2对抗氧化反应元件(are)的协同募集来控制。AhR和Nrf2成员之间的分子相互作用,以及包括I期和II期基因复合物在内的每个靶标及其介质的调控尚不清楚。方法:采用敲低AhR- nrf2组成员和强制表达AhR- nrf2组成员的方法,研究AhR- nrf2轴与AhR启动子激活之间的分子相互作用。顺序免疫沉淀,染色质免疫沉淀和组织学被用来鉴定每个蛋白复合物募集到各自的顺式元件在AhR启动子。我们检测了肌动蛋白纤维分布、细胞扩散和侵袭,以确定野生型和Jdp2敲除细胞之间AhR-Jdp2轴的功能差异。在kras - trp53驱动的突变型胰腺肿瘤中,研究了Jdp2在AhR-Nrf2轴上可能的致瘤作用。结果:在转录水平上,AhR和Nrf2之间存在明显的串扰。AhR启动子被2,3,7,8-四氯二苯并-对二恶英(TCDD)等I相配体通过AhR- jdp2 - nrf2轴以时间和空间转录依赖的方式激活。Jdp2是DRE-和are -介导的转录的双功能激活剂。暴露于TCDD后,Jdp2在DRE激活AhR启动子,然后移动到ARE,激活启动子以增加活性氧(ROS)介导的功能,如正常细胞中的细胞扩散和侵袭,以及突变的kras - trp53驱动的胰腺肿瘤细胞的癌症消退。结论:Jdp2通过AhR-Jdp2- nrf2轴在AhR启动子激活中起着重要的时空作用。在Kras-Trp53突变型胰腺癌小鼠模型中,AhR发挥维持ROS平衡、细胞扩散、侵袭和癌症消退的作用。这些发现为jp2在氧化应激的稳态调节和解毒、炎症和癌症进展中的抗氧化反应中的作用提供了新的见解。
{"title":"Jdp2 is a spatiotemporal transcriptional activator of the AhR via the Nrf2 gene battery.","authors":"Kenly Wuputra, Ming-Ho Tsai, Kohsuke Kato, Chia-Chen Ku, Jia-Bin Pan, Ya-Han Yang, Shigeo Saito, Chun-Chieh Wu, Ying-Chu Lin, Kuang-Hung Cheng, Kung-Kai Kuo, Michiya Noguchi, Yukio Nakamura, Tohru Yoshioka, Deng-Chyang Wu, Chang-Shen Lin, Kazunari K Yokoyama","doi":"10.1186/s41232-023-00290-6","DOIUrl":"10.1186/s41232-023-00290-6","url":null,"abstract":"<p><strong>Background: </strong>Crosstalk between the aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is called the \"AhR-Nrf2 gene battery\", which works synergistically in detoxification to support cell survival. Nrf2-dependent phase II gene promoters are controlled by coordinated recruitment of the AhR to adjacent dioxin responsive element (DRE) and Nrf2 recruitment to the antioxidative response element (ARE). The molecular interaction between AhR and Nrf2 members, and the regulation of each target, including phase I and II gene complexes, and their mediators are poorly understood.</p><p><strong>Methods: </strong>Knockdown and forced expression of AhR-Nrf2 battery members were used to examine the molecular interactions between the AhR-Nrf2 axis and AhR promoter activation. Sequential immunoprecipitation, chromatin immunoprecipitation, and histology were used to identify each protein complex recruited to their respective cis-elements in the AhR promoter. Actin fiber distribution, cell spreading, and invasion were examined to identify functional differences in the AhR-Jdp2 axis between wild-type and Jdp2 knockout cells. The possible tumorigenic role of Jdp2 in the AhR-Nrf2 axis was examined in mutant Kras-Trp53-driven pancreatic tumors.</p><p><strong>Results: </strong>Crosstalk between AhR and Nrf2 was evident at the transcriptional level. The AhR promoter was activated by phase I ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the AhR-Jdp2-Nrf2 axis in a time- and spatial transcription-dependent manner. Jdp2 was a bifunctional activator of DRE- and ARE-mediated transcription in response to TCDD. After TCDD exposure, Jdp2 activated the AhR promoter at the DRE and then moved to the ARE where it activated the promoter to increase reactive oxygen species (ROS)-mediated functions such as cell spreading and invasion in normal cells, and cancer regression in mutant Kras-Trp53-driven pancreatic tumor cells.</p><p><strong>Conclusions: </strong>Jdp2 plays a critical role in AhR promoter activation through the AhR-Jdp2-Nrf2 axis in a spatiotemporal manner. The AhR functions to maintain ROS balance and cell spreading, invasion, and cancer regression in a mouse model of mutant Kras-Trp53 pancreatic cancer. These findings provide new insights into the roles of Jdp2 in the homeostatic regulation of oxidative stress and in the antioxidation response in detoxification, inflammation, and cancer progression.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"43 1","pages":"42"},"PeriodicalIF":8.1,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo. Sox17下游基因Rasip1参与妊娠中期小鼠胚胎主动脉内造血簇的造血活性。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-08-08 DOI: 10.1186/s41232-023-00292-4
Gerel Melig, Ikuo Nobuhisa, Kiyoka Saito, Ryota Tsukahara, Ayumi Itabashi, Yoshiakira Kanai, Masami Kanai-Azuma, Mitsujiro Osawa, Motohiko Oshima, Atsushi Iwama, Tetsuya Taga
<p><strong>Background: </strong>During mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aorta's intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17 is expressed in IAHCs, and that, among them, CD45<sup>low</sup>c-Kit<sup>high</sup> cells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity.</p><p><strong>Methods: </strong>RNA-sequencing (RNA-seq) analysis was done to identify genes that are upregulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study, and firstly, the whole-mount immunostaining was done. We conducted luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay to examine whether Sox17 regulates Rasip1 gene expression via binding to its enhancer element. We also analyzed the cluster formation and the multilineage colony-forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells.</p><p><strong>Results: </strong>The increase of the Rasip1 expression level was observed in Sox17-positive CD45<sup>low</sup>c-Kit<sup>high</sup> cells as compared with the Sox17-nonexpressing control. Also, the expression level of the Rasip1 gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Rasip1 expression was observed in most part of c-Kit<sup>+</sup>Sox17<sup>+</sup> cells in IAHCs. Luciferase reporter assay and ChIP assay indicated that one of the five putative Sox17-binding sites in the Rasip1 enhancer region was important for Rasip1 expression via Sox17 binding. Rasip1 knockdown in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability, while overexpression of Rasip1 in CD45<sup>low</sup>c-Kit<sup>high</sup> cells led to a significant but transient increase in hematopoietic activity.</p><p><strong>Conclusions: </strong>Rasip1 knockdown in Sox17-transduced CD45<sup>low</sup>c-Kit<sup>high</sup> cells displayed a significant decrease in the multilineage colony-forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45<sup>low</sup>c-Kit<sup>high</sup> cells led to a significant but transient increase in the multilineage colony-forming ability, suggesting the presence of a cooperating factor for sustained
背景:在小鼠胚胎发育过程中,在胚胎日(E) 10.5左右,在主动脉-性腺-中肾(AGM)区域首次检测到决定性造血。造血干细胞(hsc)产生于主动脉背侧的主动脉内造血细胞簇(IAHCs)。我们之前报道过一种转录因子Sox17在IAHCs中表达,其中CD45lowc-Kithigh细胞具有较高的造血活性。此外,在这种细胞群中强制表达Sox17可以维持造血细胞簇的形成。然而,Sox17是如何做到这一点的,特别是涉及的下游信号,仍然知之甚少。本研究的目的是寻找新的Sox17靶点,这些靶点有助于形成具有造血活性的簇。方法:通过rna测序(RNA-seq)分析,鉴定表达sox17的IAHCs中与sox17阴性的IAHCs中表达上调的基因。在前7位高表达基因中,本研究重点研究了已报道的血管特异性调控基因Rasip1,首先进行了全挂载免疫染色。我们通过荧光素酶报告基因实验和染色质免疫沉淀(ChIP)实验来检测Sox17是否通过结合其增强子元件来调节Rasip1基因的表达。我们还分析了rasip1转导细胞和rasip1敲低sox17转导细胞的簇形成和多系集落形成能力。结果:与未表达sox17的对照组相比,sox17阳性CD45lowc-Kithigh细胞中Rasip1表达水平升高。此外,sox17核易位增加了Rasip1基因的表达水平。Rasip1在IAHCs的膜上表达,与内皮细胞标志物CD31和造血干细胞/祖细胞标志物c-Kit重叠。在IAHCs中,大部分c-Kit+Sox17+细胞均有Rasip1表达。荧光素酶报告基因实验和ChIP实验表明,在Rasip1增强子区域的五个推测的Sox17结合位点中,有一个对通过Sox17结合表达Rasip1很重要。在sox17转导的细胞中,Rasip1的敲低降低了簇的形成,降低了集落的形成能力,而在CD45lowc-Kithigh细胞中,Rasip1的过表达导致造血活性显著但短暂的增加。结论:在sox17转导的CD45lowc-Kithigh细胞中,Rasip1敲低显示出多系集落形成能力和簇大小的显著降低。在sox17未转导的CD45lowc-Kithigh细胞中,Rasip1过表达导致多系集落形成能力显著但短暂的增加,这表明存在一种持续造血活性的协同因子。
{"title":"A Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo.","authors":"Gerel Melig, Ikuo Nobuhisa, Kiyoka Saito, Ryota Tsukahara, Ayumi Itabashi, Yoshiakira Kanai, Masami Kanai-Azuma, Mitsujiro Osawa, Motohiko Oshima, Atsushi Iwama, Tetsuya Taga","doi":"10.1186/s41232-023-00292-4","DOIUrl":"10.1186/s41232-023-00292-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;During mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aorta's intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17 is expressed in IAHCs, and that, among them, CD45&lt;sup&gt;low&lt;/sup&gt;c-Kit&lt;sup&gt;high&lt;/sup&gt; cells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;RNA-sequencing (RNA-seq) analysis was done to identify genes that are upregulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study, and firstly, the whole-mount immunostaining was done. We conducted luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay to examine whether Sox17 regulates Rasip1 gene expression via binding to its enhancer element. We also analyzed the cluster formation and the multilineage colony-forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The increase of the Rasip1 expression level was observed in Sox17-positive CD45&lt;sup&gt;low&lt;/sup&gt;c-Kit&lt;sup&gt;high&lt;/sup&gt; cells as compared with the Sox17-nonexpressing control. Also, the expression level of the Rasip1 gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Rasip1 expression was observed in most part of c-Kit&lt;sup&gt;+&lt;/sup&gt;Sox17&lt;sup&gt;+&lt;/sup&gt; cells in IAHCs. Luciferase reporter assay and ChIP assay indicated that one of the five putative Sox17-binding sites in the Rasip1 enhancer region was important for Rasip1 expression via Sox17 binding. Rasip1 knockdown in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability, while overexpression of Rasip1 in CD45&lt;sup&gt;low&lt;/sup&gt;c-Kit&lt;sup&gt;high&lt;/sup&gt; cells led to a significant but transient increase in hematopoietic activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Rasip1 knockdown in Sox17-transduced CD45&lt;sup&gt;low&lt;/sup&gt;c-Kit&lt;sup&gt;high&lt;/sup&gt; cells displayed a significant decrease in the multilineage colony-forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45&lt;sup&gt;low&lt;/sup&gt;c-Kit&lt;sup&gt;high&lt;/sup&gt; cells led to a significant but transient increase in the multilineage colony-forming ability, suggesting the presence of a cooperating factor for sustained","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"43 1","pages":"41"},"PeriodicalIF":8.1,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A review of current status of cell-based therapies for aortic aneurysms. 细胞治疗主动脉瘤的现状综述。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-08-07 DOI: 10.1186/s41232-023-00280-8
Aika Yamawaki-Ogata, Masato Mutsuga, Yuji Narita

An aortic aneurysm (AA) is defined as focal aortic dilation that occurs mainly with older age and with chronic inflammation associated with atherosclerosis. The aneurysmal wall is a complex inflammatory environment characterized by endothelial dysfunction, macrophage activation, vascular smooth muscle cell (VSMC) apoptosis, and the production of proinflammatory molecules and matrix metalloproteases (MMPs) secreted by infiltrated inflammatory cells such as macrophages, T and B cells, dendritic cells, neutrophils, mast cells, and natural killer cells. To date, a considerable number of studies have been conducted on stem cell research, and growing evidence indicates that inflammation and tissue repair can be controlled through the functions of stem/progenitor cells. This review summarizes current cell-based therapies for AA, involving mesenchymal stem cells, VSMCs, multilineage-differentiating stress-enduring cells, and anti-inflammatory M2 macrophages. These cells produce beneficial outcomes in AA treatment by modulating the inflammatory environment, including decreasing the activity of proinflammatory molecules and MMPs, increasing anti-inflammatory molecules, modulating VSMC phenotypes, and preserving elastin. This article also describes detailed studies on pathophysiological mechanisms and the current progress of clinical trials.

主动脉瘤(AA)被定义为局灶性主动脉扩张,主要发生在老年人和与动脉粥样硬化相关的慢性炎症。动脉瘤壁是一个复杂的炎症环境,其特征是内皮功能障碍、巨噬细胞活化、血管平滑肌细胞(VSMC)凋亡,以及浸润的炎症细胞如巨噬细胞、T细胞和B细胞、树突状细胞、中性粒细胞、肥大细胞和自然杀伤细胞分泌促炎分子和基质金属蛋白酶(MMPs)。迄今为止,对干细胞的研究已经开展了相当多的研究,越来越多的证据表明,炎症和组织修复可以通过干细胞/祖细胞的功能来控制。本文综述了目前基于细胞的治疗AA的方法,包括间充质干细胞、VSMCs、多系分化应激耐受细胞和抗炎M2巨噬细胞。这些细胞通过调节炎症环境,包括降低促炎分子和MMPs的活性,增加抗炎分子,调节VSMC表型和保留弹性蛋白,在AA治疗中产生有益的结果。本文还详细介绍了其病理生理机制的研究和目前的临床试验进展。
{"title":"A review of current status of cell-based therapies for aortic aneurysms.","authors":"Aika Yamawaki-Ogata, Masato Mutsuga, Yuji Narita","doi":"10.1186/s41232-023-00280-8","DOIUrl":"10.1186/s41232-023-00280-8","url":null,"abstract":"<p><p>An aortic aneurysm (AA) is defined as focal aortic dilation that occurs mainly with older age and with chronic inflammation associated with atherosclerosis. The aneurysmal wall is a complex inflammatory environment characterized by endothelial dysfunction, macrophage activation, vascular smooth muscle cell (VSMC) apoptosis, and the production of proinflammatory molecules and matrix metalloproteases (MMPs) secreted by infiltrated inflammatory cells such as macrophages, T and B cells, dendritic cells, neutrophils, mast cells, and natural killer cells. To date, a considerable number of studies have been conducted on stem cell research, and growing evidence indicates that inflammation and tissue repair can be controlled through the functions of stem/progenitor cells. This review summarizes current cell-based therapies for AA, involving mesenchymal stem cells, VSMCs, multilineage-differentiating stress-enduring cells, and anti-inflammatory M2 macrophages. These cells produce beneficial outcomes in AA treatment by modulating the inflammatory environment, including decreasing the activity of proinflammatory molecules and MMPs, increasing anti-inflammatory molecules, modulating VSMC phenotypes, and preserving elastin. This article also describes detailed studies on pathophysiological mechanisms and the current progress of clinical trials.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"43 1","pages":"40"},"PeriodicalIF":8.1,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10405412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9959322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Autoimmune-mediated astrocytopathy. 谷蛋白astrocytopathy。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-07-18 DOI: 10.1186/s41232-023-00291-5
Makoto Kinoshita, Tatsusada Okuno

Recently accumulating evidence identified the disease entity where astrocytes residing within the central nervous system (CNS) are the target of autoantibody-mediated autoimmunity. Aquaporin4 (AQP4) is the most common antigen to serve as astrocyte-targeted autoimmune responses. Here, in this review, the clinical and pathological aspects of AQP4-mediated astrocyte disease are discussed together with the pathogenic role of anti-AQP4 antibody. More recently, the mechanism of immune dysregulation resulting in the production of astrocyte-targeted autoantibody is also revealed, and the postulated hypothesis is discussed.

最近越来越多的证据表明,中枢神经系统内的星形胶质细胞是自身抗体介导的自身免疫的目标。水通道蛋白4 (AQP4)是星形胶质细胞靶向自身免疫反应中最常见的抗原。本文就aqp4介导的星形细胞病的临床和病理方面以及抗aqp4抗体的致病作用进行综述。最近,免疫失调导致星形胶质细胞靶向自身抗体产生的机制也被揭示,并讨论了假设的假设。
{"title":"Autoimmune-mediated astrocytopathy.","authors":"Makoto Kinoshita,&nbsp;Tatsusada Okuno","doi":"10.1186/s41232-023-00291-5","DOIUrl":"https://doi.org/10.1186/s41232-023-00291-5","url":null,"abstract":"<p><p>Recently accumulating evidence identified the disease entity where astrocytes residing within the central nervous system (CNS) are the target of autoantibody-mediated autoimmunity. Aquaporin4 (AQP4) is the most common antigen to serve as astrocyte-targeted autoimmune responses. Here, in this review, the clinical and pathological aspects of AQP4-mediated astrocyte disease are discussed together with the pathogenic role of anti-AQP4 antibody. More recently, the mechanism of immune dysregulation resulting in the production of astrocyte-targeted autoantibody is also revealed, and the postulated hypothesis is discussed.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"43 1","pages":"39"},"PeriodicalIF":8.1,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9833625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipid in microglial biology - from material to mediator. 小胶质细胞生物学中的脂质——从物质到介质。
IF 8.1 3区 医学 Q2 IMMUNOLOGY Pub Date : 2023-07-17 DOI: 10.1186/s41232-023-00289-z
Shota Yamamoto, Takahiro Masuda

Microglia are resident macrophages in the central nervous system (CNS) that play various roles during brain development and in the pathogenesis of CNS diseases. Recently, reprogramming of cellular energetic metabolism in microglia has drawn attention as a crucial mechanism for diversification of microglial functionality. Lipids are highly diverse materials and crucial components of cell membranes in every cell. Accumulating evidence has shown that lipid and its metabolism are tightly involved in microglial biology. In this review, we summarize the current knowledge about microglial lipid metabolism in health and disease.

小胶质细胞是中枢神经系统(CNS)中的巨噬细胞,在大脑发育和中枢神经系统疾病的发病过程中发挥着多种作用。近年来,小胶质细胞能量代谢的重编程被认为是小胶质细胞功能多样化的重要机制。脂质是高度多样化的物质,是每个细胞中细胞膜的重要组成部分。越来越多的证据表明,脂质及其代谢与小胶质细胞生物学密切相关。本文就小胶质细胞脂质代谢在健康和疾病中的作用作一综述。
{"title":"Lipid in microglial biology - from material to mediator.","authors":"Shota Yamamoto,&nbsp;Takahiro Masuda","doi":"10.1186/s41232-023-00289-z","DOIUrl":"https://doi.org/10.1186/s41232-023-00289-z","url":null,"abstract":"<p><p>Microglia are resident macrophages in the central nervous system (CNS) that play various roles during brain development and in the pathogenesis of CNS diseases. Recently, reprogramming of cellular energetic metabolism in microglia has drawn attention as a crucial mechanism for diversification of microglial functionality. Lipids are highly diverse materials and crucial components of cell membranes in every cell. Accumulating evidence has shown that lipid and its metabolism are tightly involved in microglial biology. In this review, we summarize the current knowledge about microglial lipid metabolism in health and disease.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"43 1","pages":"38"},"PeriodicalIF":8.1,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Inflammation and Regeneration
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