Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts.
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.
Nakayama
Seiko
S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Mukae
Hiroshi
H
Sakamoto
Noriho
N
Kakugawa
Tomoyuki
T
Yoshioka
Sumako
S
Soda
Hiroshi
H
Oku
Hisashi
H
Urata
Yoshie
Y
Kondo
Takahito
T
Kubota
Hiroshi
H
Nagata
Kazuhiro
K
Kohno
Shigeru
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D050958:HSP47 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D050958:HSP47 Heat-Shock Proteins; D011728:Pyridones; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C093844:pirfenidone