MiR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy

Shawn S. Badal, Yin Wang, Jianyin Long, David L. Corcoran, Benny H. Chang, Luan D. Truong, Yashpal S. Kanwar, Paul A. Overbeek, Farhad R. Danesh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish (US)
Article number12076
JournalNature communications
Volume7
DOIs
StatePublished - Jun 28 2016

Funding

This work was supported by NIH Grants RO1DK091310 and RO1DK078900 (F.R.D), and T32GM088129 (S.S.B). Work performed by the UT-MDACC high-resolution microscopy facility was supported by Institutional funds (Core Grant CA16672). High-throughput sequencing data was generated by the UT-MDACC Sequencing and Microarray Facility (Core Grant CA016672 SMF).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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