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Copyright ©ERS Journals Ltd 2004
Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis
1 Second Dept of Internal Medicine, Nagasaki University School of Medicine, 2 Dept of Pathology, Nagasaki University Hospital, Nagasaki, and 3 Medicinal Biology 3 Division, Discovery Research Laboratories, Shionogi & Co. Ltd, Osaka, and 4 Second Dept of Internal Medicine, Oita Medical University, Oita, Japan
CORRESPONDENCE: H. Mukae, Second Dept of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. Fax: 81 958497285. E-mail: hmukae@net.nagasaki-u.ac.jp
Keywords: Heat shock protein 47, myofibroblast, pirfenidone, pulmonary fibrosis, 
-smooth muscle actin
Received: October 28, 2003
Accepted March 9, 2004
This study was supported in part by a research grant from the Ministry of Education, Science, Sports and Culture of Japan.
Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. The present study was undertaken to investigate whether treatment with the antifibrotic drug pirfenidone attenuates the bleomycin (BL)-induced overexpression of HSP47 in the lungs.
Male ICR mice were intravenously injected with BL or saline (SA). Pirfenidone or control drug (CD) was administered 14 days after commencement of BL or SA, and continued throughout the course of the experiment. The mice were randomly divided into three experimental groups: 1) SA-treated with CD (SA group); 2) BL-treated with CD (BL group); and 3) BL-treated with pirfenidone (pirfenidone group).
Lungs of the pirfenidone group showed a marked reduction of fibrotic lesions compared with the corresponding BL group. Immunohistochemical studies showed that BL treatment significantly increased the number of macrophages, myofibroblasts, HSP47-positive type II pneumocytes and HSP47-positive interstitial spindle-shaped cells. Treatment with pirfenidone significantly reduced the number of these cells compared with the corresponding BL group. Furthermore, treatment with pirfenidone significantly suppressed the BL-induced increase of the positive ratio of HSP47 and
The present study results showed that pirfenidone inhibited heat shock protein 47-positive cells and myofibroblasts, the principal cells responsible for the accumulation and deposition of extracellular matrix seen in pulmonary fibrosis.
-smooth muscle actin to interstitial spindle-shaped cells.
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