Differential expression of collagen- and laminin-binding integrins mediates ureteric bud and inner medullary collecting duct cell tubulogenesis
Differential expression of collagen- and laminin-binding integrins mediates ureteric bud and inner medullary collecting duct cell tubulogenesis
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DOI：
10.1152/ajprenal.00015.2004
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发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Zent, R
中科院分区：
文献类型：
--
作者：
Chen, D;Roberts, R;Zent, R
内髓集合管（IMCD）是起源于输尿管芽（UB）的终末分化结构。UB的发展是由整合素及其各自配体的时空表达变化介导的。我们在体内和体外均证实UB主要表达层粘连蛋白受体（α（3）β（1）-、α（6）β（1）-和α（6）β（4）-整联蛋白），而IMCD表达胶原（α（1）β（1）-和α（2）β（1）-整联蛋白）和层粘连蛋白受体。来自IMCD而非UB的细胞以α（1）β（1）-和α（2）β（1）-依赖性方式在胶原蛋白-I（CI）凝胶中发生小管生成。UB细胞转染α（2）-整联蛋白亚基进行微管在CI，表明胶原受体所需的分支形态发生在CI。相比之下，UB和IMCD细胞在CI/Matrigel凝胶中均经历小管形成。UB细胞主要利用α（3）β（1）-和α（6）-整联蛋白，而IMCD细胞主要利用α（1）β（1）进行该过程。这些结果表明，整合素表达从早期UB中的主要层粘连蛋白受体转换为成熟IMCD中的胶原蛋白和层粘连蛋白受体，这对三维细胞培养模型中的分支形态发生具有功能性后果。这表明整合素表达的时间和空间变化有助于组织体内发育中的收集系统的分支形态发生模式。
Inner medullary collecting ducts (IMCD) are terminally differentiated structures derived from the ureteric bud (UB). UB development is mediated by changes in the temporal and spatial expression of integrins and their respective ligands. We demonstrate both in vivo and in vitro that the UB expresses predominantly laminin receptors (alpha(3)beta(1)-, alpha(6)beta(1)-, and alpha(6)beta(4)-integrins), whereas the IMCD expresses both collagen (alpha(1)beta(1)- and alpha(2)beta(1)-integrins) and laminin receptors. Cells derived from the IMCD, but not the UB, undergo tubulogenesis in collagen-I (CI) gels in an alpha(1)beta(1)- and alpha(2)beta(1)-dependent manner. UB cells transfected with the alpha(2)-integrin subunit undergo tubulogenesis in CI, suggesting that collagen receptors are required for branching morphogenesis in CI. In contrast, both UB and IMCD cells undergo tubulogenesis in CI/Matrigel gels. UB cells primarily utilize alpha(3)beta(1)- and alpha(6)-integrins, whereas IMCD cells mainly employ alpha(1)beta(1) for this process. These results demonstrate a switch in integrin expression from primarily laminin receptors in the early UB to both collagen and laminin receptors in the mature IMCD, which has functional consequences for branching morphogenesis in three-dimensional cell culture models. This suggests that temporal and spatial changes in integrin expression could help organize the pattern of branching morphogenesis of the developing collecting system in vivo.