Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud
Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud
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DOI：
10.1073/pnas.221205198
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发表时间：
2001-10-23
影响因子：
11.1
通讯作者：
Cantley, LG
中科院分区：
文献类型：
--
作者：
Karihaloo, A;Karumanchi, SA;Cantley, LG
内皮抑素 (ES) 抑制内皮细胞迁移，并被发现与内皮细胞和肾上皮细胞上的磷脂酰肌醇蛋白聚糖 (Gpcs) 结合。我们研究了 ES 可能调节上皮细胞形态发生的可能性。将 ES 添加到培养的上皮细胞中会抑制肝细胞生长因子和表皮生长因子依赖性过程的形成和迁移。相反，ES不会抑制来自Gpc-3-/小鼠的肾上皮细胞中表皮生长因子依赖性形态发生，而这些细胞中Gpc-1的表达重建了ES反应性。 Gpc-3 -/小鼠已被证明在发育早期表现出增强的输尿管芽 (UB) 分支，并且培养的 UB 细胞将 ES 释放到培养基中，表明 ES 与 Gpc 的结合可能调节 UB 分支。添加 ES 可抑制外植 UB 的分支，而 ES 的中和抗体可增强 UB 的生长和分支。因此，ES在UB尖端的局部表达可能在UB树枝化的调节中发挥作用。
Endostatin (ES) inhibits endothelial cell migration and has been found to bind to glypicans (Gpcs) on both endothelial cells and renal epithelial cells. We examined the possibility that ES might regulate epithelial cell morphogenesis. The addition of ES to cultured epithelial cells causes an inhibition of both hepatocyte growth factor- and epidermal growth factor-dependent process formation and migration. In contrast, ES does not inhibit epidermal growth factor-dependent morphogenesis in renal epithelial cells derived from Gpc-3 -/mice, whereas expression of Gpc-1 in these cells reconstitutes ES responsiveness. Gpc-3 -/mice have been shown to display enhanced ureteric bud (UB) branching early in development, and cultured UB cells release ES into the media, suggesting that ES binding to Gpcs may regulate UB branching. The addition of ES inhibits branching of the explanted UB, whereas a neutralizing Ab to ES enhances UB outgrowth and branching. Thus, local expression of ES at the tips of the UB may play a role in the regulation of UB arborization.