MicroRNA-21 in scleroderma fibrosis and its function in TGF-β-regulated fibrosis-related genes expression

J Clin Immunol. 2013 Aug;33(6):1100-9. doi: 10.1007/s10875-013-9896-z. Epub 2013 May 9.


Uncontrolled fibrosis in multiple organs is the main cause of death in systemic sclerosis (SSc), and transforming growth factor-β (TGF-β) activation plays a fundamental role in the process. Our previous study demonstrated that miR-21 was significantly up-regulated in SSc fibroblasts. Here, we found that TGF-β regulated the expression of miR-21 and fibrosis-related genes, and decreased Smad7 expression. Over-expression of miR-21 in fibroblasts decreased the levels of Smad7, whereas knockdown of miR-21 increased its expression. Further study using a reporter gene assay demonstrated Smad7 was a direct target of miR-21. Similar to human SSc, the expression of miR-21 increased in the bleomycin induced skin fibrosis. Inhibition of fibrosis by treatment with anti-fibrosis drug bortezomib restored the levels of miR-21 and Smad7. MiR-21 may function in an amplifying circuit to enhance TGF-β signaling events in SSc fibrosis, and suggesting that miR-21 may act as a potential therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / metabolism
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cells, Cultured
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibrosis
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Mice, Inbred DBA
  • MicroRNAs / metabolism*
  • Molecular Targeted Therapy
  • Pyrazines / pharmacology
  • RNA, Small Interfering / genetics
  • Scleroderma, Diffuse / drug therapy
  • Scleroderma, Diffuse / genetics*
  • Scleroderma, Diffuse / pathology*
  • Signal Transduction
  • Skin / pathology
  • Smad7 Protein / genetics*
  • Transforming Growth Factor beta / metabolism*


  • Boronic Acids
  • MIRN21 microRNA, human
  • MicroRNAs
  • Pyrazines
  • RNA, Small Interfering
  • Smad7 Protein
  • Transforming Growth Factor beta
  • Bleomycin
  • Bortezomib