ALTERATIONS IN PULMONARY MESSENGER-RNA ENCODING PROCOLLAGENS, FIBRONECTIN AND TRANSFORMING GROWTH FACTOR-BETA PRECEDE BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN MICE

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  • 1 August 1988
    • journal article
    • research article
    • Vol. 246  (2) , 765-771
Abstract
Female C57Bl/6 mice treated by constant s.c. infusion for 1 week with 100 mg of bleomycin per kg of body weight develop a more pronounced pulmonary fibrosis than BALB/C mice. Within 4 weeks after bleomycin treatment, the pulmonary content of mRNAs encoding fibronectin, .alpha.2I procollagen and .alpha.1III procollagen was increased. The increases were greater and occurred earlier in C57Bl/6 mice compared to BALB/c mice. Fibronectin mRNA increased 12-fold in C57Bl/6 mice and only 3-fold in BALB/c mice, whereas .alpha.1III procollagen mRNA increased 4-fold in C57Bl/6 mice and 2-fold in BALB/c mice. .alpha.2I procollagen mRNA was increased only in C57Bl/6 mice (2-fold). The increases were sequential in C57Bl/6 mice: fibronectin mRNA was elevated first, followed by .alpha.2I procollagen, then .alpha.1III procollagen mRNA. The temporal relationship between these mRNA elevations and extracellular matrix accumulation, and the exaggerated responses in C57Bl/6 mice, suggest that matrix accumulation is a function of the mRNA levels. Transforming growth factor-.beta.m RNA relative to total polyadenylated RNA was elevated 5-fold in C57Bl/6 mice and depressed 80% in BALBc mice 1 week after treatment. Early alterations in transforming growth factor-.beta. mRNA may contribute to murine strain variation in bleomycin-induced pulmonary fibrosis and suggest the involvement of transforming growth factor-.beta. in this disease.