Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts

Life Sci. 2008 Jan 16;82(3-4):210-7. doi: 10.1016/j.lfs.2007.11.003. Epub 2007 Nov 23.


Pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and patients with idiopathic pulmonary fibrosis (IPF). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen and plays an important role in the pathogenesis of IPF. The present study evaluated the in vitro effects of pirfenidone on expression of HSP47 and collagen type I in cultured normal human lung fibroblasts (NHLF). Expression levels of HSP47 and collagen type I in NHLF stimulated by transforming growth factor (TGF)-beta1 were evaluated genetically, immunologically and immunocytochemically. Treatment with TGF-beta1 stimulated both mRNA and protein expressions of both HSP47 and collagen type I in NHLF, and pirfenidone significantly inhibited this TGF-beta1-enhanced expression in a dose-dependent manner. We concluded that the anti-fibrotic effect of pirfenidone may be mediated not only through direct inhibition of collagen type I expression but also at least partly through inhibition of HSP47 expression in lung fibroblasts, with a resultant reduction of collagen synthesis in lung fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • Collagen Type I / antagonists & inhibitors
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Fibroblasts / drug effects*
  • Fibroblasts / pathology
  • Gene Expression / drug effects*
  • HSP47 Heat-Shock Proteins / antagonists & inhibitors
  • HSP47 Heat-Shock Proteins / genetics
  • HSP47 Heat-Shock Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Lung / drug effects*
  • Lung / pathology
  • Pyridones / pharmacology*
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta1 / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Collagen Type I
  • HSP47 Heat-Shock Proteins
  • Pyridones
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • pirfenidone