Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47

Virchows Arch. 1998 May;432(5):455-60. doi: 10.1007/s004280050191.


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.

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Bleomycin
  • Collagen / metabolism
  • HSP47 Heat-Shock Proteins
  • Heat-Shock Proteins / metabolism*
  • Immunohistochemistry
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Rats
  • Rats, Wistar


  • Anti-Bacterial Agents
  • HSP47 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Serpinh1 protein, rat
  • Bleomycin
  • Collagen