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

Author

Listed:
  • Shawn S. Badal

    (Section of Nephrology, The University of Texas MD Anderson Cancer Center
    Baylor College of Medicine)

  • Yin Wang

    (Section of Nephrology, The University of Texas MD Anderson Cancer Center)

  • Jianyin Long

    (Section of Nephrology, The University of Texas MD Anderson Cancer Center)

  • David L. Corcoran

    (Center for Genomic and Computational Biology, Duke University)

  • Benny H. Chang

    (Baylor College of Medicine)

  • Luan D. Truong

    (Houston Methodist Hospital
    6565 Fannin Street)

  • Yashpal S. Kanwar

    (Feinberg School of Medicine, Northwestern University)

  • Paul A. Overbeek

    (Baylor College of Medicine)

  • Farhad R. Danesh

    (Section of Nephrology, The University of Texas MD Anderson Cancer Center
    Baylor College of Medicine
    Baylor College of Medicine)

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.

Suggested Citation

  • 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, 2016. "miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12076
    DOI: 10.1038/ncomms12076
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