Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4

The syndecans make up a family of transmembrane heparan sulfate proteoglyca ns that act as coreceptors with integrins and growth factor tyrosine kinase receptors. Syndecan-4 is upregulated in skin dermis after wounding, and, i n cultured fibroblasts adherent to the ECM protein fibronectin, this proteo glycan signals cooperatively with beta (1) integrins. In this study, we gen erated mice in which the syndecan-4 gene was disrupted by homologous recomb ination in embryonic stem cells to test the hypothesis that syndecan-4 cont ributes 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 heter ozygous or homozygous for the disrupted gene have statistically significant delayed healing of skin wounds and impaired angiogenesis in the granulatio n tissue. These results indicate that syndecan-4 is an important cell-surfa ce receptor in wound healing and angiogenesis and that syndecan-4 is haplo- insufficient in these processes.