EPITHELIAL BRANCHING MORPHOGENESIS AND ENDOSTATIN

描述(改编自申请人？S摘要)：内皮抑素(ES)，a XVIII胶原蛋白的C末端片段已被证明显著抑制生长 因子介导的内皮细胞迁移、增殖和小管形成 但还没有在上皮细胞中进行研究。ES存在于胚胎中 肾脏，也是由输尿管芽细胞组成。描述的初步数据 在这项建议中揭示了ES与上皮细胞结合并抑制HGF 刺激单个细胞的迁移和分枝形态发生 胶原蛋白凝胶基质。此外，ES还抑制了AN大鼠输尿管芽的分枝。 体外培养，表明ES可能在胚胎干细胞的发育过程中起重要作用。 UB，因此还有肾脏。目前，ES？S效应的作用机制尚不清楚。这 本研究旨在探讨ES？S在上皮细胞中的作用机制 通过检测MAPK、PI13-Kinase和PLC等不同信号通路对细胞的影响 已知在上皮形态发生中起关键作用的是伽玛。此外，这个角色 将利用建立的体外UB培养来探索UB发育中的胚胎干细胞。

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.