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

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Title: Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts.
Authors: Nakayama, Seiko / Mukae, Hiroshi / Sakamoto, Noriho / Kakugawa, Tomoyuki / Yoshioka, Sumako / Soda, Hiroshi / Oku, Hisashi / Urata, Yoshie / Kondo, Takahito / Kubota, Hiroshi / Nagata, Kazuhiro / Kohno, Shigeru
Issue Date: 16-Jan-2008
Publisher: Elsevier Inc.
Citation: Life sciences, 82(3-4), pp.210-217; 2008
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.
Keywords: Collagen type I / Fibroblast / Heat shock protein 47 (HSP47) / Idiopathic pulmonary fibrosis / Lung fibrosis / Pirfenidone
URI: http://hdl.handle.net/10069/23124
ISSN: 00243205
DOI: 10.1016/j.lfs.2007.11.003
PubMed ID: 18093617
Rights: Copyright © 2007 Elsevier Inc. All rights reserved.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/23124

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