Abstract

PDGF isoforms are a family of polypeptides that bind to cell surface receptors and induce fibroblast proliferation and chemotaxis. The PDGF-A and -B chain isoforms have been implicated in fibroproliferative lung injury in animal models and in human disease. Two recently recognized PDGF polypeptides, PDGF-C and -D, differ from the PDGF-A and -B isoforms in that they require proteolytic cleavage before they can bind and activate the PDGF receptors. Our findings demonstrate that administration of bleomycin to murine lungs leads to a significant increase in PDGF-C mRNA expression and a significant decrease in PDGF-D mRNA expression. PDGF-C expression was localized to areas of lung injury by in situ hybridization, and PDGF-C expression was not upregulated in the lungs of BALB/c mice that are resistant to bleomycin-induced lung fibrosis. Moreover, there is in vivo phosphorylation of the PDGF-receptor that binds PDGF-C in response to bleomycin administration. These observations strongly suggest a role for PDGF-C in bleomycin-induced pulmonary fibrosis.