STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy.

Ye Tian, Zhenhua Bi, Shuaina Ge, Bo Ye, Wenjie Han

Clinical and experimental pharmacology & physiology 2022 Jun

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Diabetic nephropathy (DN), one of microvascular complications of diabetes mellitus, results in renal dysfunction and end-stage renal disease. Recently, endothelial-to-mesenchymal transition (EndMT) was reported to mediate glomerular endothelial dysfunction, therefore, participating in the progress of fibrosis in DN. As a special type of epithelial-to-mesenchymal transition, EndMT and epithelial-to-mesenchymal transition may share corporate modulators. It was reported that epidermal growth factor (EGF), latrophilin and seven transmembrane domain containing 1 (ELTD1) and signal transducer and activator of transcription 5A (STAT5A) participate in epithelial-to-mesenchymal transition in some situations. In this work, we proposed that STAT5A participated in high glucose-mediated EndMT via modulation of ELTD1 levels in DN. Our data indicated that hyperglycemia/high glucose-induced ELTD1 and EndMT in DN rats and hyperglycemic human glomerular endothelial cells (HGECs). Additionally, high glucose mediated STAT5A nuclear translocation in HGECs. High glucose-mediated EndMT was reversed by ELTD1 silencing. Moreover, STAT5A was found to be elevated in DN rats and hyperglycemic HGECs. The effect of high glucose-mediated increase of ELTD1 expression and EndMT was reversed by STAT5A silencing in vitro. Further, STAT5A overexpression enhanced ELTD1 levels and EndMT, which was inhibited by si-ELTD1. Chromatin immunoprecipitation (ChIP) and luciferase assay represented that STAT5A directly regulated ELTD1 transcription. Signal transducer and activator of transcription 5A directly regulated ELTD1 transcription, therefore, participating in high glucose-mediated EndMT in glomeruli of DN. © 2022 John Wiley & Sons Australia, Ltd.

Citation

Ye Tian, Zhenhua Bi, Shuaina Ge, Bo Ye, Wenjie Han. STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy. Clinical and experimental pharmacology & physiology. 2022 Jun;49(6):686-695