Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4
Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4
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DOI：
10.1172/jci10559
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发表时间：
2001-01-01
影响因子：
15.9
通讯作者：
Goetinck, PF
中科院分区：
文献类型：
--
作者：
Echtermeyer, F;Streit, M;Goetinck, PF
Syndecans组成了一个跨膜硫酸乙酰肝素蛋白多糖家族，与整合素和生长因子酪氨酸激酶受体起辅助受体的作用。Syndecan-4在创伤后的皮肤真皮中上调，在贴附ECM蛋白纤维连接蛋白的培养成纤维细胞中，这种蛋白多糖与β(1)整合素协同信号。在这项研究中，我们产生了胚胎干细胞中Syndecan-4基因被同源重组破坏的小鼠，以验证Syndecan-4有助于伤口修复的假设。突变的syndecan-4基因的杂合子或纯合子的小鼠是存活的、有生育能力的，从宏观上看与野生型小鼠没有区别。与野生型小鼠相比，突变基因的杂合子或纯合子的小鼠皮肤伤口愈合延迟，肉芽组织中的血管生成受损。这些结果表明，Syndecan-4是伤口愈合和血管生成过程中重要的细胞表面受体，而Syndecan-4在这些过程中缺乏。
The syndecans make up a family of transmembrane heparan sulfate proteoglycans that act as coreceptors with integrins and growth factor tyrosine kinase receptors. Syndecan-4 is upregulated in skin dermis after wounding, and, in cultured fibroblasts adherent to the ECM protein fibronectin, this proteoglycan signals cooperatively with beta (1) integrins. In this study, we generated mice in which the syndecan-4 gene was disrupted by homologous recombination in embryonic stem cells to test the hypothesis that syndecan-4 contributes to wound repair. Mice heterozygous or homozygous for the disrupted syndecan-4 gene are viable, fertile, and macroscopically indistinguishable from wild-type littermates. Compared with wild-type littermates, mice heterozygous or homozygous for the disrupted gene have statistically significant delayed healing of skin wounds and impaired angiogenesis in the granulation tissue. These results indicate that syndecan-4 is an important cell-surface receptor in wound healing and angiogenesis and that syndecan-4 is haplo-insufficient in these processes.