Early increases in pulmonary mRNA encoding procollagens and transforming growth factor-beta in mice sensitive to cyclophosphamide-induced pulmonary fibrosis.
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.
Hoyt
D G
DG
Department of Pharmacology, University of Pittsburgh, School of Medicine, Pennsylvania.
Lazo
J S
JS
D000818:Animals; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011347:Procollagen / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D013045:Species Specificity; D015291:Transforming Growth Factors / Q000235:genetics*
D011347:Procollagen; D012333:RNA, Messenger; D015291:Transforming Growth Factors; D003520:Cyclophosphamide