Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice.
Constant 7-day subcutaneous infusion of bleomycin (100 mg/kg) induces pulmonary fibrosis in C57Bl/6N mice, whereas BALB/cN mice are relatively resistant. In contrast, cyclophosphamide (200 mg/kg, ip) induces fibrosis in BALB/cN mice, whereas C57Bl/6N mice are resistant. The effect of these drugs on the pulmonary levels of mRNA encoding the major basement membrane components, laminin and type IV collagen, relative to poly (A+)RNA was determined in both C57Bl/6N and BALB/cN mice. In the sensitive C57Bl/6N mice, bleomycin increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the absence of increases in laminin A, B1, and B2 mRNA/poly (A+)RNA. In the relatively resistant BALB/cN mice, bleomycin did not alter alpha 1IV procollagen mRNA/poly (A+)RNA and only transiently increased laminin A, B1, B2, and alpha 2IV procollagen mRNA/poly (A+)RNA. Similarly, cyclophosphamide increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the sensitive BALB/cN mice and not in C57Bl/6N mice. Laminin mRNAs/poly (A+)RNA were not increased by cyclophosphamide in either strain. Thus, in these models, pulmonary fibrosis is preceded by a coordinate increase in steady-state levels of mRNA encoding basement membrane procollagen but is not associated with an increase in laminin gene expression.
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
D G
DG
Hoyt
J S
JS
Lazo
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D015342:DNA Probes; D005260:Female; D007700:Kinetics; D007797:Laminin / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009693:Nucleic Acid Hybridization; D011061:Poly A / Q000235:genetics; D011347:Procollagen / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*
D015342:DNA Probes; D007797:Laminin; D011347:Procollagen; D012333:RNA, Messenger; D001761:Bleomycin; D011061:Poly A; D012313:RNA; D003520:Cyclophosphamide