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Early increases in pulmonary mRNA encoding procollagens and transforming growth factor-beta in mice sensitive to cyclophosphamide- induced pulmonary fibrosis

DG Hoyt and JS Lazo

Department of Pharmacology, University of Pittsburgh, School of Medicine, Pennsylvania.

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 1III procollagen, and transforming growth factor-beta. In BALB/c mice, the ratios of alpha 2I and alpha 1III 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.

Volume 249, Issue 1, pp. 38-43, 04/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1989 by the American Society for Pharmacology and Experimental Therapeutics.