miR-34c attenuates epithelial-mesenchymal transition and kidney fibrosis with ureteral obstruction

Sci Rep. 2014 Apr 3:4:4578. doi: 10.1038/srep04578.

Abstract

micro RNAs (miRNAs) are small non-coding RNAs that act as posttranscriptional repressors by binding to the 3'-UTR of target mRNAs. On the other hand, mesenchymal-epithelial transition (EMT) and kidney fibrosis is a pathological process of chronic kidney disease (CKD), and its relationship to miRNAs is becoming recognized as a potential target for CKD therapies. To find new miRNAs involved in EMT, we examined miRNA expression in experimental models of EMT and renal epithelialization using microarray, and found that miR-34c attenuates EMT induced by TGF-β in a mouse tubular cell line. To confirm the effects of miR-34c in vivo, we administered the precursor of miR-34c to mice with unilateral ureteral obstruction, and miR-34c decreased kidney fibrosis area and the expression of connective tissue growth factor, α-SMA, collagen type 1, collagen type 3 and fibronectin. In conclusion, our study showed miR-34c attenuates EMT and kidney fibrosis of mice with ureteral obstruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Calcium-Binding Proteins / metabolism
  • Cell Line
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Epithelial-Mesenchymal Transition* / drug effects
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fibrosis
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kidney / metabolism
  • Kidney / pathology
  • Membrane Proteins / metabolism
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotides, Antisense / metabolism
  • Serrate-Jagged Proteins
  • Transforming Growth Factor beta / pharmacology
  • Ureteral Obstruction / genetics
  • Ureteral Obstruction / pathology*

Substances

  • Acta2 protein, mouse
  • Actins
  • Calcium-Binding Proteins
  • Collagen Type I
  • Collagen Type III
  • Fibronectins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Serrate-Jagged Proteins
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor

Associated data

  • GEO/GSE42719