Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47.
Increased accumulation of collagens in extracellular matrix (ECM) is mainly responsible for bleomycin-induced pulmonary fibrosis in rats. This study was designed to assess whether increased collagen accumulation in bleomycin-induced pulmonary fibrosis is associated with heat shock protein (HSP) 47, a molecular chaperone for collagen biosynthesis. We investigated the expression of type I and type III collagens and HSP47 in bleomycin-induced pulmonary fibrosis. Fifteen male Wistar rats were divided into two groups; group I: bleomycin-induced pulmonary fibrosis; group II: PBS-treated age-matched control rats. Pulmonary fibrosis was induced by injecting a single dose of bleomycin sulphate (5 U/kg body weight) intratracheally. Three bleomycin-treated rats and two age-matched control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of the experiment. In bleomycin-treated rats, histological examination revealed pulmonary fibrosis, which increased with time. Increased type I and type III collagen desposition was observed in the lungs of all the bleomycin-treated rats. Weak immunostaining of HSP47 was noted in the control lungs. In contrast, strong immunostaining for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In addition, increased numbers of phenotypically altered myofibroblasts (alpha-smooth muscle actin immunopositive) and fibroblast (vimentin immunopositive) were seen in bleomycin-treated lungs and found to express HSP47. Parallel increase of collagens and their molecular chaperone HSP47 expression was found in the bleomycin-treated lungs, and their co-localization could be detected by double immunostaining. Overexpression of HSP47 may play a significant part in the excessive assembly of collagens and could contribute in this way to the fibrosis found in bleomycin-treated rat lungs.
Razzaque
M S
MS
Second Department of Pathology, Nagasaki University School of Medicine, Sakamoto, Japan. razzaque@net.nagasaki-u.ac.jp
Hossain
M A
MA
Kohno
S
S
Taguchi
T
T
D000818:Animals; D000900:Anti-Bacterial Agents; D001761:Bleomycin; D003094:Collagen / Q000378:metabolism; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494662:Serpinh1 protein, rat; D001761:Bleomycin; D003094:Collagen