PDGFRα plays a crucial role in connective tissue remodeling.
PDGFRα plays a crucial role in connective tissue remodeling.
复制标题
DOI：
10.1038/srep17948
复制
发表时间：
2015-12-07
影响因子：
4.6
通讯作者：
Sasahara M
中科院分区：
文献类型：
--
作者：
Horikawa S;Ishii Y;Hamashima T;Yamamoto S;Mori H;Fujimori T;Shen J;Inoue R;Nishizono H;Itoh H;Majima M;Abraham D;Miyawaki T;Sasahara M
血小板源性生长因子（PDGF）在结缔组织重塑中起着关键作用。新出现的数据表明PDGF受体-α（PDGFRα）在这一过程中的独特作用。在本研究中，在成年小鼠（α-KO小鼠）中系统失活Pdgfra基因，并在皮下植入的海绵基质中检测PDGFRα的作用。PDGFRα在Pdgfra保留对照小鼠（Flox小鼠）的成纤维细胞中表达，在α-KO小鼠的海绵中显著降低。与Flox小鼠相比，α-KO小鼠的新生血管化区域受到很大程度的抑制，而与血管和内皮细胞相关的其他参数相似。α-KO小鼠的胶原和纤维连接蛋白沉积以及胶原1a 1和3a 1基因的表达明显减少。α-KO小鼠的成纤维细胞数量和分裂能力明显下降，而巨噬细胞的数量和分裂能力在两种基因型之间相似。肝细胞生长因子（Hgf）基因的表达被抑制在Pdgfra灭活的成纤维细胞和结缔组织。这些发现暗示了成纤维细胞中PDGFRα依赖性ECM和HGF的产生在促进结缔组织重塑中的作用，并表明PDGFRα可能是调节结缔组织重塑的相关靶点。
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.