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 H(2)O(2)-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(2)O(2)-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.