PDGFRα plays a crucial role in connective tissue remodeling

Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-alpha (PDGFR alpha) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (alpha-KO mouse), and the role of PDGFR alpha was examined in the subcutaneously implanted sponge matrices. PDGFR alpha expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in alpha-KO mice. Neovascularized areas were largely suppressed in the alpha-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in alpha-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the alpha-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFR alpha-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFR alpha may be a relevant target to regulate connective tissue remodeling.