Increased type I procollagen mRNA transcripts in the lungs of mice during the development of bleomycin-induced fibrosis

Abstract

In this study, in situ hybridization has been used to investigate the localization of type I procollagen messenger ribonucleic acid (mRNA) in normal lung, and in the lungs of mice during the development of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced by a single intratracheal instillation of bleomycin sulphate (6 mg.kg-1 body weight), and tissues examined at times up to 35 days thereafter. Tissue transcripts of alpha 2(I) procollagen mRNA were visualized after hybridization with 35S-labelled riboprobes. Hybridization signals were associated with alveolar interstitial cells throughout the normal lung, with additional areas of dense hybridization signals observed subpleurally. Three days following administration of bleomycin, there was no apparent change in the pattern of hybridization. By 10 days, foci of intense hybridization signals indicative of gene activation were observed associated with individual cells in the alveolar interstitium. At 21 days, the increase in hybridization signals appeared to be associated with greater numbers of cells rather than highly activated cells. These results demonstrate that procollagen genes are normally expressed in the mouse lung, and that during bleomycin-induced pulmonary fibrosis hybridization signals increase, suggesting that both enhanced gene expression by individual cells and increased numbers of cells expressing the type I procollagen gene are involved in the pathogenetic mechanism.