MiR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy Academic Article uri icon

Overview

MeSH Major

  • Basement Membrane
  • Glomerulonephritis
  • Kidney Glomerulus
  • Nephrotic Syndrome
  • Proteinuria

abstract

  • How the kidney responds to the metabolic cues from the environment remains a central question in kidney research. This question is particularly relevant to the pathogenesis of diabetic nephropathy (DN) in which evidence suggests that metabolic events in podocytes regulate chromatin structure. Here, we show that miR-93 is a critical metabolic/epigenetic switch in the diabetic milieu linking the metabolic state to chromatin remodelling. Mice with inducible overexpression of a miR-93 transgene exclusively in podocytes exhibit significant improvements in key features of DN. We identify miR-93 as a regulator of nucleosomal dynamics in podocytes. miR-93 has a critical role in chromatin reorganization and progression of DN by modulating its target Msk2, a histone kinase, and its substrate H3S10. These findings implicate a central role for miR-93 in high glucose-induced chromatin remodelling in the kidney, and provide evidence for a previously unrecognized role for Msk2 as a target for DN therapy.

publication date

  • June 28, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4931323

Digital Object Identifier (DOI)

  • 10.1038/ncomms12076

PubMed ID

  • 27350436

Additional Document Info

start page

  • 12076

volume

  • 7