Animal model shows TRIM27 promotes GLIS1 expression in renal tubular epithelial cells, indicating a pathway for AKI recovery.
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.
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Xiong et al. (2025) studied this question.