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 m ainly responsible for bleomycin-induced pulmonary fibrosis in rats. Th is study was designed to assess whether increased collagen accumulatio n in bleomycin-induced pulmonary fibrosis is associated with heat shoc k protein (HSP) 47, a molecular chaperone for collagen biosynthesis. W e investigated the expression of type I and type III collagens and HSP 47 in bleomycin-induced pulmonary fibrosis. Fifteen male Wistar rats w ere divided into two groups; group I: bleomycin-induced pulmonary fibr osis; group II: PBS-treated age-matched central rats. Pulmonary fibros is was induced by injecting a single dose of bleomycin sulphate (5 U/k g body weight) intratracheally. Three bleomycin-treated rats and two a ge-matched control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of the experiment. In bleomycin-treated rats, histo logical 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 immunostain ing for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In addition, increased numbers of phenotypically altered myofibroblasts (a-smooth muscle actin immunopositive) and fibroblast (vimentin immuno positive) were seen in bleomycin-treated lungs and found to express HS P47. Parallel increase of collagens and their molecular chaperone HSP4 7 expression was found in the bleomycin-treated lungs, and their co-lo calization could be detected by double immunostaining. Overexpression of HSP47 may play a significant part in the excessive assembly of coll agens and could contribute in this way to the fibrosis found in bleomy cin-treated rat lungs.