MicroRNA-770-5p contributes to podocyte injury via targeting E2F3 in diabetic nephropathy

MicroRNA-770-5p contributes to podocyte injury via targeting E2F3 in diabetic nephropathy

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Diabetic nephropathy (DN) has been identified as the major cause of end-stage renal disease (ESRD) in most developed countries.MicroRNA-770-5p depletion could repress high glucose (HG)-triggered apoptosis in podocytes, and downregulation of E2F transcription factor 3 (E2F3) could facilitate podocyte injury.Nevertheless, whether E2F3 is involved in miR-770-5p knockdown-mediated improvement of DN is still unclear.The expression levels of miR-770-5p and E2F3 were detected in HG-treated podocytes by RT-qPCR.

The expression levels of E2F3, apoptosis-related proteins eagles head coach hoodie Bcl-2 related X protein (Bax), B-cell lymphoma-2 (Bcl-2), Bad, apoptotic peptidase activating factor 1 (APAF1), C-caspase3, C-caspase7, and C-caspase9 were detected by western blot assay.The effects of miR-770-5p and E2F3 on HG-treated podocytes proliferation and apoptosis were detected by CCK-8 and flow cytometry assays.The interaction between miR-770-5p and E2F3 was predicted by Targetscan, and then verified by the dual-luciferase reporter assay.MiR-770-5p was upregulated and E2F3 was downregulated in HG-treated podocytes.

MiR-770-5p inhibited proliferation and here promoted apoptosis and E2F3 promoted proliferation and suppressed apoptosis in HG-treated podocytes.E2F3 is a target gene of miR-770-5p and it partially abolished the effect of miR-770-5p in HG-triggered proliferation and apoptosis of podocytes.MiR-770-5p deficiency blocked HG-induced APAF1/caspase9 pathway via targeting E2F3 in podocytes.We firstly confirmed that E2F3 was a target of miR-770-5p in podocytes.

These findings suggested that miR-770-5p expedited podocyte injury by targeting E2F3, and the miR-770-5p/E2F3 axis might represent a pathological mechanism of DN progression.