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Am J Physiol Lung Cell Mol Physiol 285: L957-L963, 2003. First published July 3, 2003; doi:10.1152/ajplung.00305.2002
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Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy

Hiroshi Ishii,1 Hiroshi Mukae,1 Tomoyuki Kakugawa,1 Tetsuji Iwashita,1 Hideyuki Kaida,1 Takeshi Fujii,1 Tomayoshi Hayashi,2 Jun-ichi Kadota,3 and Shigeru Kohno1

1Second Department of Internal Medicine, Nagasaki University School of Medicine, 2Department of Pathology, Nagasaki University Hospital, Nagasaki 852-850; and 3Second Department of Internal Medicine, Oita Medical University, Oita 879-5593, Japan

Submitted 11 September 2002 ; accepted in final form 2 July 2003

The 47-kDa heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the processing and/or secretion of procollagen. Expression of HSP47 has been reported to increase in parallel with expression of collagens during the progression of various fibrosis models. The aim of the present study was to investigate the association between HSP47 expression and collagen accumulation in bleomycin (BLM)-induced murine fibrosis. We investigated the expression of HSP47 protein and mRNA using immunohistochemical analysis and semi-quantitative RT-PCR in murine BLM-induced pulmonary fibrosis. Immunohistochemical analysis showed that higher expression of HSP47 protein was present in BLM-induced pulmonary fibrosis compared with controls. HSP47 was localized predominantly in {alpha}-smooth muscle actin-positive myofibroblasts, F4/80 negative, surfactant protein-A-positive type II pneumocytes, and F4/80-positive macrophages. RT-PCR also demonstrated an increase of HSP47 mRNA expression in BLM-treated lungs. Moreover, the relative amounts of HSP47 mRNA correlated significantly with the lung hydroxyproline content as an indicator of pulmonary fibrosis in BLM-treated lungs (r = 0.406, P <0.05). Our results suggest that these cells may play a role in the fibrotic process of BLM-treated lungs through upregulation of HSP47.

pulmonary fibrosis; bleomycin


Address for reprint requests and other correspondence: H. Mukae, Second Dept. of Internal Medicine, Nagasaki Univ. School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan, 852-8501 (E-mail: hmukae{at}net.nagasaki-u.ac.jp).




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T. Kakugawa, H. Mukae, T. Hayashi, H. Ishii, K. Abe, T. Fujii, H. Oku, M. Miyazaki, J. Kadota, and S. Kohno
Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis
Eur. Respir. J., July 1, 2004; 24(1): 57 - 65.
[Abstract] [Full Text] [PDF]


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