MicroRNA‐503 contributes to podocyte injury via targeting E2F3 in diabetic nephropathy

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. K E Y W O R D Sdiabetic nephropathy, E2F transcription factor 3, miR-503

MicroRNA‑199a‑3p suppresses high glucose‑induced apoptosis and inflammation by regulating the IKKβ/NF‑κB signaling pathway in renal tubular epithelial cells

“…1B ). Among these aberrantly expressed miRNAs, miR-146a, miR-214 and miR-503 were increased, which was consistent with previous reports ( 6 , 20 , 21 ), indicating the reliability of the present microarray. Of the downregulated miRNAs, miR-199a-3p was identified as one of the most significantly downregulated.…”

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

“…In terms of apoptosis and cell death, miR-503 expression was higher in DN mice, and it negatively inhibits the expression of E2F transcription factor 3 (E2f3), and E2f3 is the transcription factor that is involved in the regulation of cell apoptosis, differentiation, and development (Zha et al, 2019). Reduction of the E2f3 expression leads to podocyte cells apoptosis and injury, induced by high glucose (Zha et al, 2019).…”

“…In terms of apoptosis and cell death, miR-503 expression was higher in DN mice, and it negatively inhibits the expression of E2F transcription factor 3 (E2f3), and E2f3 is the transcription factor that is involved in the regulation of cell apoptosis, differentiation, and development (Zha et al, 2019). Reduction of the E2f3 expression leads to podocyte cells apoptosis and injury, induced by high glucose (Zha et al, 2019). Importantly, in the mice model of DN treated with Losartan (a drug for kidney disease treatment), the prevention of DN progression in those mice was evident with the inhibition of miR-503 action (Zhu et al, 2016), therefore confirming the role of miR-503 in contributing to podocyte cell death.…”

GRB10 and E2F3 as Diagnostic Markers of Osteoarthritis and Their Correlation with Immune Infiltration

“…A study has shown that E2F3 plays a key role in muscle and bone development and affects the normal growth of mice [34]. Inhibition of E2F3 expression promotes the development of diabetic nephropathy [35]. Furthermore, E2F3 plays a key role in various biological processes such as lens development, cardiac neovascularization, DNA damage response, and neuronal migration [36][37][38][39].…”