EARLY INCREASES IN PULMONARY MESSENGER-RNA ENCODING PROCOLLAGENS AND TRANSFORMING GROWTH FACTOR-BETA IN MICE SENSITIVE TO CYCLOPHOSPHAMIDE-INDUCED PULMONARY FIBROSIS

  • 1 April 1989
    • journal article
    • research article
    • Vol. 249  (1) , 38-43
Abstract
Pulmonary fibrosis was induced 7 weeks after a single i.p. injection of cyclophosphamide (200 mg/kg b.wt.) in BALB/c mice; C57Bl/6 mice were unaffected. There was a corresponding strain variation in the effects of cyclophosphamide on levels of pulmonary mRNA encoding .alpha.2I and .alpha.1 III procollagen, and transforming growth factor-.beta.. In BALB/c mice, the ratios of .alpha.2I and .alpha.1 III procollagen mRNA to polyadenylated RNA were increased 1 week after cyclophosphamide injection. No increases in levels of either procollagen mRNA occurred in C57Bl/6 mice. The ratio of fibronectin mRNA to polyadenylated RNA was elevated to a similar extent in both murine strains during the 1st week after cyclophosphamide treatment. The pulmonary content of transforming growth factor-.beta. mRNA and its ratio to polyadenylated RNA increased 2-fold at 1 and 2 weeks in BALB/c but not C57Bl/6 mice. Thus, collagen accumulation in cyclophosphamide-sensitive mice is preceded by increased pulmonary .alpha.2I and .alpha.1III procollagen mRNA. The early strain selective elevation of transforming growth factor-.beta. mRNA in response to cyclophosphamide suggests a role, in vivo, for transforming growth factor-.beta. in drug-induced pulmonary fibrosis.

This publication has 1 reference indexed in Scilit: