EPITHELIAL BRANCHING MORPHOGENESIS AND ENDOSTATIN

描述（改编自申请人？内皮抑制素（Endostatin，ES）是一种 胶原蛋白XVIII的C-末端片段已显示出显著抑制生长 因子介导的内皮细胞迁移、增殖和小管形成 但尚未在上皮细胞中进行研究。ES存在于胚胎中 肾脏也由输尿管芽细胞构成。初步数据显示， 在该提议中揭示了ES结合上皮细胞并抑制HGF 刺激单个细胞的迁移和分支形态发生， 胶原凝胶基质。此外，ES抑制了小鼠输尿管芽的分支， 离体培养，表明ES可能是重要的发展， UB和肾脏。目前，ES的作用机制尚不清楚。的影响是未知的。这 建议的目的是探讨机制ES？在上皮细胞中的作用 通过检测MAPK、PI 13-激酶和PLC等各种信号通路， γ，已知在上皮形态发生中至关重要。此外，作用 将使用离体UB培养装置探索ES在UB发育中的作用。

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.