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

Abstract

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.

• Authors: Seiko Nakayama, Hiroshi Mukae, Noriho Sakamoto, Tomoyuki Kakugawa, Sumako Yoshioka, Hiroshi Soda, Hisashi Oku, Yoshie Urata, Takahito Kondo, Hiroshi Kubota, Kazuhiro Nagata, Shigeru Kohno
• Journal: Life sciences (Life Sci) Vol. 82 Issue 3-4 Pg. 210-7 (Jan 16 2008) ISSN: 0024-3205 [Print] Netherlands
• PMID: 18093617 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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