MicroRNA‐503 contributes to podocyte injury via targeting E2F3 in diabetic nephropathy. Issue 8 (4th March 2019)

• Record Type: Journal Article
• Authors: Zha, Fangfang; Bai, Lin; Tang, Bo; Li, Ji; Wang, Yakun; Zheng, PengXi; Ji, Tingting; Bai, Shoujun
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 8(2019)
• Page Start: 12574
• Page End: 12581
• Publication Date: 2019-03-04
• Subjects: diabetic nephropathy -- E2F transcription factor 3 -- miR‐503; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28524
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Diabetic nephropathy (DN) is serious diabetic complication with capillary injury. Podocyte injury exerts a crucial effect on DN pathogenesis. MicroRNA‐503 (miR‐503) has been reported in various diseases including DN. Here, we investigated the detailed mechanism of miR‐503 in the podocyte injury of DN. The functional role of miR‐503 was investigated in cultured podocytes and diabetic rats. Podocyte injury was evaluated by migration and apoptosis experiments in podocytes and we observed that high glucose elevated miR‐503 in a time and dose‐dependent manner. Meanwhile, E2F transcription factor 3 (E2F3), as a crucial regulator in multiple diseases, was predicted as a potential target of miR‐503 here. It was shown that E2F3 was greatly decreased in podocytes incubated with high glucose and miR‐503 modulated its expression negatively. In addition, downregulation of E2F3 contributed to podocyte injury, which was reversed by miR‐503 inhibitors in vitro. Furthermore, we proved that increase of miR‐503 resulted in an unfavorable renal function in diabetic rats via targeting E2F3. These revealed for the first time that the overexpression of miR‐503 promoted podocyte injury via targeting E2F3 in diabetic nephropathy and miR‐503/E2F3 axis might represent a pathological mechanism of diabetic nephropathy progression. Abstract : We found that E2F transcription factor 3 (E2F3) was greatly decreased in DM both in vitro and in vivo. E2F3 acted as a direct target of miR‐503 and it could be regulated by miR‐503 negatively, and knockdown of E2F3 was able to induce podocyte injury, which was reversed by miR‐503 inhibitors. It is the first time to uncover that miR‐503 might serve as a biomarker and therapeutic target in diabetic nephropathy (DN) via targeting E2F3.