Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice

Am J Physiol. 1990 Aug;259(2 Pt 1):L47-52. doi: 10.1152/ajplung.1990.259.2.L47.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bleomycin / pharmacology*
  • Cyclophosphamide / pharmacology*
  • DNA Probes
  • Female
  • Kinetics
  • Laminin / genetics
  • Lung / drug effects
  • Lung / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nucleic Acid Hybridization
  • Poly A / genetics
  • Procollagen / genetics*
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics*

Substances

  • DNA Probes
  • Laminin
  • Procollagen
  • RNA, Messenger
  • Bleomycin
  • Poly A
  • RNA
  • Cyclophosphamide