INCREASED TYPE-I PROCOLLAGEN MESSENGER-RNA TRANSCRIPTS IN THE LUNGS OF MICE DURING THE DEVELOPMENT OF BLEOMYCIN-INDUCED FIBROSIS

In this study, in situ hybridization has been used to investigate the localization of type I procollagen messenger ribonucleic acid (mRNA) i n normal lung, and in the lungs of mice during the development of bleo mycin-induced pulmonary fibrosis. Lung fibrosis was induced by a singl e intratracheal instillation of bleomycin sulphate (6 mg.kg(-1) body w eight), and tissues examined at times up to 35 days thereafter. Tissue transcripts of alpha(2)(I) procollagen mRNA were visualized after hyb ridization with S-35-labelled riboprobes. Hybridization signals were a ssociated with alveolar interstitial cells throughout the normal lung, with additional areas of dense hybridization signals observed subpleu rally. Three days following administration of bleomycin, there was no apparent change in the pattern of hybridization. By 10 days, foci of i ntense hybridization signals indicative of gene activation were observ ed associated with individual cells in the alveolar interstitium. At 2 1 days, the increase in hybridization signals appeared to be associate d with greater numbers of cells rather than highly activated cells. Th ese results demonstrate that procollagen genes are normally expressed in the mouse lung, and that during bleomycin-induced pulmonary fibrosi s hybridization signals increase, suggesting that both enhanced gene e xpression by individual cells and increased numbers of cells expressin g the type I procollagen gene are involved in the pathogenetic mechani sm.