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

Abstract

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 HGtreated podocytes by RT-qPCR. The expression levels of E2F3, apoptosis-related proteins 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 HGtreated podocytes. MiR-770-5p inhibited proliferation and 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.

The Potential Diagnostic Value of Immune-Related Genes in Interstitial Fibrosis and Tubular Atrophy after Kidney Transplantation

“…Moreover, has-mir-136-5p can improve renal fibrosis by targeting SYK and inhibition of TGF-β1/Smad3 signaling pathway [40]. has-mir-770-5p can cause podocyte injury via targeting E2F3 in diabetic nephropathy [41]. However, the relationship between other microRNAs and renal dysfunction needs further investigations.…”

MicroRNA‐17‐5p restrains the dysfunction of Ang‐II induced podocytes by suppressing secreted modular calcium‐binding protein 2 via NF‐κB and TGFβ signaling

“…For example, miRNA‐27a facilitates podocyte injury through the activation of β‐catenin in diabetic nephropathy 32 . MiRNA‐770‐5p promotes podocyte injury through E2F3 in diabetic nephropathy 33 . MiRNA‐204‐3p serves as a protective role for podocytes against high glucose‐induced cell apoptosis 34 .…”

“…32 MiRNA-770-5p promotes podocyte injury through E2F3 in diabetic nephropathy. 33 MiRNA-204-3p serves as a protective role for podocytes against high glucose-induced cell apoptosis. 34 Importantly, miRNA-17 has proved to be downregulated in the plasma of focal segmental glomerulosclerosis.…”

miRNA‑770‑5p expression is upregulated in patients with type 2 diabetes and miRNA‑770‑5p knockdown protects pancreatic β‑cell function via targeting BAG5 expression

“…It has been reported that miRNAs serve important roles in the development of islet cell failure in patients with T2DM (9). miR-770-5p is a form of mature miR-770and the high evolutionary conservation of miR-770-5p suggests that it may be of particular biological significance (10). Several studies have demonstrated that miR-770 is clinically significant and serves a crucial role in the carcinogenesis and progression of different types of cancer, such as non-small cell lung, breast, ovarian and gastric cancer, as well as hepatocellular carcinoma (11)(12)(13)(14)(15).…”