The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy

Sci Rep. 2016 Nov 22:6:37492. doi: 10.1038/srep37492.

Abstract

MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Bioinformatic analyses and luciferase assays further demonstrated that both miR-26a and miR-30c targeted connective tissue growth factor (CTGF); additionally, Snail family zinc finger 1 (Snail1), a potent epithelial-to-mesenchymal transition (EMT) inducer, was targeted by miR-30c. Overexpression of miR-26a and miR-30c coordinately decreased CTGF protein levels and subsequently ameliorated TGFβ1-induced EMT in NRK-52E cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect. Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK activation. Furthermore, miR-26a was up-regulated in urinary extracellular vesicles of diabetic nephropathy patients. Our study provides evidence for the cooperative roles of miR-26a and miR-30c in the pathogenesis of diabetic nephropathy, and the co-targeting of miR-26a and miR-30c could provide a new direction for diabetic nephropathy treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Connective Tissue Growth Factor / metabolism
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / pathology*
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Extracellular Vesicles / drug effects
  • Extracellular Vesicles / metabolism
  • Fibrosis
  • Humans
  • MicroRNAs / metabolism*
  • Models, Biological
  • Rats
  • Rats, Inbred OLETF
  • Signal Transduction / drug effects
  • Snail Family Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • Up-Regulation / drug effects

Substances

  • MIRN26 microRNA, rat
  • MIRN26A microRNA, human
  • MIRN30 microRNA, rat
  • MIRN30b microRNA, human
  • MicroRNAs
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor