期刊
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
卷 49, 期 6, 页码 686-695出版社
WILEY
DOI: 10.1111/1440-1681.13644
关键词
ELTD1; EndMT; STAT5A
资金
- science and technology boost fund [2020KTB07]
This study reveals the involvement of endothelial-to-mesenchymal transition (EndMT) in diabetic nephropathy (DN) and its connection with epithelial-to-mesenchymal transition. By modulating the levels of ELTD1, STAT5A participates in high glucose-mediated EndMT in DN.
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.
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