title: PDGFRα plays a crucial role in connective tissue remodeling.
abstract: 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.
authors.affiliation: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.|Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Horikawa
authors.affiliation: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Hamashima
authors.affiliation: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
authors.affiliation: Division of Embryology, National Institute for Basic Biology, Okazaki 444-8787, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujimori
authors.affiliation: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Inoue
authors.affiliation: Division of Animal Experimental Laboratory, Life Science Research Center, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nishizono
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Department of Pharmacology, School of Medicine, Kitasato University, Kanagawa 252-0374, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Majima
authors.affiliation: Division of Medicine, University College London, Royal Free Campus, London, NW3 2PF, UK.
authors.forename: David
authors.initials: D
authors.lastname: Abraham
authors.affiliation: Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.affiliation: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sasahara
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D020007:Implants, Experimental; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D013629:Tamoxifen; D017228:Hepatocyte Growth Factor; D003094:Collagen; D020796:Receptor, Platelet-Derived Growth Factor alpha