MicroRNA-130a Targets MAP3K12 to Modulate Diabetic Endothelial Progenitor Cell Function

Cell Physiol Biochem. 2015;36(2):712-26. doi: 10.1159/000430132.

Abstract

Aims: The aim of the present study was to explore the influence of microRNA (miR)-130a dysregulation on the JNK signal pathway through its target MAP3K12 in diabetic endothelial progenitor cells (EPCs).

Methods: The expression of miR-130a was compared between diabetic and normal EPCs. Computational target prediction was performed to identify MAP3K12 as a functionally relevant target of miR-130a in EPCs. The role of miR-130a was investigated regarding its anti-apoptotic effects and its role on the regulation of EPC function was evaluated through the negative regulation of the JNK signal pathway

Results: MiR-130a expression was significantly downregulated in diabetic EPCs, and cell proliferation was reduced in EPCs under high glucose condition. miR-130a inhibited the JNK pathway by targeting MAP3K12, contributing to its anti-apoptotic effect and the maintenance of EPC function. In diabetic EPCs, high glucose affects the expression of miR-130a, inducing sustained JNK activation and promoting EPC apoptosis and dysfunction.

Conclusions: Downregulation of miR-130a may underlie endothelial dysfunction in diabetes through the activation of JNK signal pathway.

MeSH terms

  • Aged
  • Apoptosis
  • Cell Proliferation
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Down-Regulation
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / pathology*
  • Female
  • Humans
  • MAP Kinase Kinase Kinases / genetics*
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Up-Regulation

Substances

  • MIRN130 microRNA, human
  • MicroRNAs
  • MAP Kinase Kinase Kinases
  • mitogen-activated protein kinase kinase kinase 12