microRNA-20b contributes to high glucose-induced podocyte apoptosis by targeting SIRT7

Mol Med Rep. 2017 Oct;16(4):5667-5674. doi: 10.3892/mmr.2017.7224. Epub 2017 Aug 10.

Abstract

Previous reports have indicated that microRNAs (miRNAs) have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte apoptosis induced by high glucose (HG) is characteristic of DN. However, the role of miRNAs in HG‑induced podocyte apoptosis remains poorly understood. The present study investigated the role and potential underlying mechanism of miRNA‑20b (miR‑20b) in podocyte apoptosis induced by HG. The results demonstrated that miR‑20b was significantly upregulated in HG‑treated podocytes, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Caspase‑3 activity and TUNEL assays indicated that suppression of miR‑20b using miR‑20b inhibitors significantly inhibited the podocyte apoptosis induced by HG. Sirtuin 7 (SIRT7) was identified as a functional target of miR‑20b by a Dual‑Luciferase activity reporter assay, RT‑qPCR and western blot analysis. Silencing SIRT7 promoted HG‑induced podocyte apoptosis, as determined by the caspase‑3 activity, while SIRT7 overexpression attenuated HG‑induced podocyte apoptosis. However, SIRT7 silencing significantly blocked the protective effect of miR‑20b suppression against HG‑induced apoptosis. In conclusion, these results indicate that miR‑20b may contribute to HG‑induced podocyte apoptosis by targeting SIRT7, providing a potential therapeutic target for the treatment of DN.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Caspase 3 / metabolism
  • Cell Line, Transformed
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Podocytes / metabolism*
  • RNA Interference*
  • Sirtuins / genetics*

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Mirn20 microRNA, mouse
  • Sirt7 protein, mouse
  • Caspase 3
  • Sirtuins
  • Glucose