INTEGRINS IN KIDNEY MORPHOGENESIS

描述：(改编自申请人的摘要)-整合素和 层粘连蛋白对肾小管上皮细胞的形态发生至关重要。 在发育过程中，整合素与层粘连蛋白和其他 细胞外基质蛋白是上皮-间充质形成所必需的 早期上皮的相互作用、极化和分化 沿肾单位的单个细胞类型。在成人体内，整合素锚定 细胞到基板由不同的层粘连蛋白同工型组成。 与整合素的去极化一起破坏这些相互作用 是急性肾功能衰竭和其他疾病发病机制中的重要步骤 疾病过程。随着肾小管上皮细胞的再生，整合素和 层粘连蛋白无疑是随后重新分化的主要因素。在……里面 在项目的这一部分，调查人员建议继续研究 整合素和细胞外基质蛋白在肾脏中的作用 形态发生。特别是，实验旨在增加一个 了解整合素在损伤、再生和修复过程中的作用 肾小管上皮细胞在分子水平的分化。 在特定目标1中，对整合素的调节进行了研究 肾细胞系的配体结合活性、表达和分布 受到ATP的限制，将进行耗尽。此外，基准面 将识别整合素中的靶向信号，以及整合素的分布 在缺血大鼠肾脏中整合素α和β亚基将 检查过了。 在特异靶2中，Forssman抗原在层粘连蛋白黏附中的作用 极化和形态发生将通过重建进行检查 研究、生物检测和反义方法。的表达方式 肾小管囊形成过程中及形成后肾细胞系的层粘连蛋白亚型 机械损伤，而在缺血后大鼠肾脏也会 下定决心。最后，整合素和层粘连蛋白在上皮细胞中的参与 细胞极化将通过表达反义和 显性-否定结构。

DESCRIPTION: (Adapted from the applicant's abstract) - Integrins and laminin are crucial for morphogenesis of the kidney tubular epithelium. During development, integrins interacting with laminin and other extracellular matrix proteins are essential for epithelial-mesenchymal interactions, polarization of the early epithelium, and differentiation of individual cell types along the nephron. In the adult, integrins anchor cells to the basal lamina composed of different laminin isotypes. Disruption of these interactions together with depolarization of integrins are important steps in the pathogenesis of acute renal failure and other disease processes. As the tubular epithelium regenerates, integrins and laminin are undoubtedly major factors in the ensuing redifferentiation. In this part of the project, the investigators propose to continue studies on the roles of integrins and extracellular matrix proteins in kidney morphogenesis. In particular, experiments are designed to increase an understanding of integrin function during injury, regeneration, and differentiation of kidney tubular epithelial cells at the molecular level. In Specific Aim 1, an examination of the modulation of integrin ligand-binding activity, expression, and distribution in kidney cell lines subjected to ATP-depletion will be carried out. In addition, basolateral targeting signals in integrins will be identified, and the distribution of integrin alpha and beta subunits in the ischemic rat kidney will be examined. In Specific Aim 2, the role of Forssman antigen in laminin adhesion, cell polarization, and morphogenesis will be examined through reconstitution studies, biological assays, and antisense approaches. The expression of laminin isotypes in kidney cell lines during tubulocyst formation and after mechanical injury, and in the post-ischemic rat kidney will also be determined. Finally, the involvement of integrins and laminin in epithelial cell polarization will be tested through the expression of antisense and dominant-negative constructs.