Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy.
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.
Ishii
Hiroshi
H
Second Dept. of Internal Medicine, Nagasaki Univ. School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan, 852-8501.
Mukae
Hiroshi
H
Kakugawa
Tomoyuki
T
Iwashita
Tetsuji
T
Kaida
Hideyuki
H
Fujii
Takeshi
T
Hayashi
Tomayoshi
T
Kadota
Jun-Ichi
J
Kohno
Shigeru
S
D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D003094:Collagen / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C494661:Serpinh1 protein, mouse; D001761:Bleomycin; D003094:Collagen