Chongxiang Xiong, Haishan Chen, Baoting Su, Li Zhang, Jingxiang Hu, Qiaowen Wang, Shougang Zhuang
{"title":"三结构域蛋白27通过抑制多梳抑制复合体2活性，促进胶质样转录因子1的表达，从而减轻缺血再灌注损伤引起的急性肾损伤","authors":"Chongxiang Xiong, Haishan Chen, Baoting Su, Li Zhang, Jingxiang Hu, Qiaowen Wang, Shougang Zhuang","doi":"10.1002/ccs3.70046","DOIUrl":null,"url":null,"abstract":"<p>Dedifferentiated renal tubular epithelial cell (RTEC) proliferation contributes to renal repair following acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) injury (RIRI). However, the fundamental mechanism underlying RTEC dedifferentiation remains unclear. An animal model of RIRI-induced AKI was established using I/R, and H<sub>2</sub>O<sub>2</sub>-treated murine (m) RTECs were used as the cell injury model. Pathological changes were assessed by hematoxylin and eosin and periodic acid–Schiff stain staining. Cell viability and migration were assessed using the cell counting kit-8 and wound healing assays, respectively. Apoptosis was examined using flow cytometry. Molecular interactions were investigated using coimmunoprecipitation and chromatin IP assays. Tri-domain proteins 27 (TRIM27) expression was reduced in RIRI mice and H<sub>2</sub>O<sub>2</sub>-treated mouse renal tubular epithelial cells (mRTECs). TRIM27 overexpression enhanced mRTECs dedifferentiation, proliferation, and migration while inhibiting apoptosis. Mechanistically, TRIM27 reduced polycomb repressive complex 2 (PRC2) activity in mRTECs through the mediation of Enhancer of zeste homolog 2 ubiquitination. Further, PRC2 reduced Gli-like transcription factor 1 (GLIS1) expression in mRTECs by regulating Histone H3 trimethylated at lysine 27 and DNA methylation. TRIM27 overexpression ameliorated RIRI-induced AKI in mice by enhancing mRTEC dedifferentiation. TRIM27 upregulation alleviates RIRI-induced AKI by reducing GLIS1 DNA methylation and promoting GLIS1 expression by inhibiting PRC2 activity.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"19 3","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70046","citationCount":"0","resultStr":"{\"title\":\"Tri-domain proteins 27 alleviates ischemia-reperfusion injury-induced acute kidney injury by promoting Gli-like transcription factor 1 expression via the inhibition of polycomb repressive complex 2 activity\",\"authors\":\"Chongxiang Xiong, Haishan Chen, Baoting Su, Li Zhang, Jingxiang Hu, Qiaowen Wang, Shougang Zhuang\",\"doi\":\"10.1002/ccs3.70046\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Dedifferentiated renal tubular epithelial cell (RTEC) proliferation contributes to renal repair following acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) injury (RIRI). However, the fundamental mechanism underlying RTEC dedifferentiation remains unclear. An animal model of RIRI-induced AKI was established using I/R, and H<sub>2</sub>O<sub>2</sub>-treated murine (m) RTECs were used as the cell injury model. Pathological changes were assessed by hematoxylin and eosin and periodic acid–Schiff stain staining. Cell viability and migration were assessed using the cell counting kit-8 and wound healing assays, respectively. Apoptosis was examined using flow cytometry. Molecular interactions were investigated using coimmunoprecipitation and chromatin IP assays. Tri-domain proteins 27 (TRIM27) expression was reduced in RIRI mice and H<sub>2</sub>O<sub>2</sub>-treated mouse renal tubular epithelial cells (mRTECs). TRIM27 overexpression enhanced mRTECs dedifferentiation, proliferation, and migration while inhibiting apoptosis. Mechanistically, TRIM27 reduced polycomb repressive complex 2 (PRC2) activity in mRTECs through the mediation of Enhancer of zeste homolog 2 ubiquitination. Further, PRC2 reduced Gli-like transcription factor 1 (GLIS1) expression in mRTECs by regulating Histone H3 trimethylated at lysine 27 and DNA methylation. TRIM27 overexpression ameliorated RIRI-induced AKI in mice by enhancing mRTEC dedifferentiation. 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Tri-domain proteins 27 alleviates ischemia-reperfusion injury-induced acute kidney injury by promoting Gli-like transcription factor 1 expression via the inhibition of polycomb repressive complex 2 activity
Dedifferentiated renal tubular epithelial cell (RTEC) proliferation contributes to renal repair following acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) injury (RIRI). However, the fundamental mechanism underlying RTEC dedifferentiation remains unclear. An animal model of RIRI-induced AKI was established using I/R, and H2O2-treated murine (m) RTECs were used as the cell injury model. Pathological changes were assessed by hematoxylin and eosin and periodic acid–Schiff stain staining. Cell viability and migration were assessed using the cell counting kit-8 and wound healing assays, respectively. Apoptosis was examined using flow cytometry. Molecular interactions were investigated using coimmunoprecipitation and chromatin IP assays. Tri-domain proteins 27 (TRIM27) expression was reduced in RIRI mice and H2O2-treated mouse renal tubular epithelial cells (mRTECs). TRIM27 overexpression enhanced mRTECs dedifferentiation, proliferation, and migration while inhibiting apoptosis. Mechanistically, TRIM27 reduced polycomb repressive complex 2 (PRC2) activity in mRTECs through the mediation of Enhancer of zeste homolog 2 ubiquitination. Further, PRC2 reduced Gli-like transcription factor 1 (GLIS1) expression in mRTECs by regulating Histone H3 trimethylated at lysine 27 and DNA methylation. TRIM27 overexpression ameliorated RIRI-induced AKI in mice by enhancing mRTEC dedifferentiation. TRIM27 upregulation alleviates RIRI-induced AKI by reducing GLIS1 DNA methylation and promoting GLIS1 expression by inhibiting PRC2 activity.
期刊介绍：
The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies.
Research manuscripts can be published under two different sections :
In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research.
In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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