EPITHELIAL BRANCHING MORPHOGENESIS AND ENDOSTATIN

描述(改编自申请人？【摘要】：内皮抑素（ES）

DESCRIPTION (Adapted from the Applicant?s Abstract): Endostatin (ES), a C-terminal fragment of collagen XVIII has been shown to markedly inhibit growth factor mediated endothelial cell migration, proliferation, and tubule formation but has not been explored in epithelial cells. ES is present in embryonic kidney and is also made by ureteric bud cells. The preliminary data described in this proposal reveal that ES binds to epithelial cells and inhibits HGF stimulated migration and branching morphogenesis of individual cells in collagen gel matrix. In addition, ES inhibited branching of ureteric bud in an ex-vivo culture, indicating that ES may be important in the development of the UB and hence kidney. At present the mechanism of ES?s effect is unknown. This proposal is designed to explored the mechanism of ES?s action in epithelial cells by examining various signaling pathways such at MAPK, PI13-kinase and PLC gamma, known to be critical in epithelial morphogenesis. In addition, the role of ES in UB development will be explored using an ex-vivo UB culture set up.