PDGFRα plays a crucial role in connective tissue remodeling

• Published in: Scientific reports Vol. 5; no. 1; p. 17948
• Main Authors: Horikawa, Shinjiro, Ishii, Yoko, Hamashima, Takeru, Yamamoto, Seiji, Mori, Hisashi, Fujimori, Toshihiko, Shen, Jie, Inoue, Ran, Nishizono, Hirofumi, Itoh, Hiroshi, Majima, Masataka, Abraham, David, Miyawaki, Toshio, Sasahara, Masakiyo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.12.2015; Nature Publishing Group
• Subjects: 14; 14/63; 38/77; 631/80/84/750; 631/80/86/2368; 64/60; 82/51; 96/35; Animals; Blood Vessels - drug effects; Blood Vessels - metabolism; Cell Count; Collagen - metabolism; Connective Tissue - drug effects; Connective Tissue - metabolism; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibronectins - metabolism; Fluorescent Antibody Technique; Hepatocyte Growth Factor - metabolism; Humanities and Social Sciences; Implants, Experimental; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Neovascularization, Physiologic - drug effects; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Science; Skin - cytology; Tamoxifen - pharmacology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep17948

Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse) and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra -preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-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 α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-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 PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.