Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2552925 | Life Sciences | 2008 | 8 Pages |
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)-β1 were evaluated genetically, immunologically and immunocytochemically. Treatment with TGF-β1 stimulated both mRNA and protein expressions of both HSP47 and collagen type I in NHLF, and pirfenidone significantly inhibited this TGF-β1-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.
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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,