INTEGRIN AND CADHERIN IN POLYCYSTIC KIDNEY DISEASE

多囊肾病（PKD）的特征是肾小管中正常上皮细胞形态和功能的丧失，以及由此产生的囊肿形成。因此，多囊蛋白1和2是维持正常上皮形态和功能所需的分子组。在我们的实验室中，一个主要的焦点是整合素和钙粘蛋白，通常被认为是细胞-细胞外基质（ECM）和细胞-细胞粘附分子，分别合作，以维持正常的上皮形态。作为这些研究的一部分，我们最近发表了α β 1整联蛋白，除了其作为层粘连蛋白（ECM的一种组分）的受体的作用外，还作为粘附连接的一部分发挥作用，在粘附连接中，α β 1整联蛋白与钙粘蛋白：连环蛋白复合物结合，并刺激钙粘蛋白介导的细胞-细胞粘附。在这项研究中，我们现在将重点放在整合素和钙粘蛋白在PKD中的作用，特别是多囊蛋白1和2如何在影响整合素和钙粘蛋白功能的信号转导途径中发挥作用。了解整合素和钙粘素在PKD中的作用可能最终导致改善囊肿形成的药物干预。PKD是导致透析和移植的慢性肾衰竭的重要部分的原因。这项研究旨在了解PKD如何导致肾损伤，将产生信息，应该导致 有助于预防PKD肾损伤的治疗。

Polycystic kidney disease (PKD) is characterized by loss of normal epithelial morphology and function in kidney tubules, and resultant cyst formation. Polycystins 1 and 2 are, therefore, among the groups of molecules required to maintain normal epithelial morphology and function. In our laboratory, a major focus has been on how integrins and cadherins, normally thought of as cell-extracellular matrix (ECM) and cell-cell adhesion molecules, respectively, cooperate to maintain normal epithelial morphology. As a component of these studies, we have recently published that alphas betal integrin, apart from its role as a receptor for laminin, a component of the ECM, also functions as part of the adherens junction where it associates with the cadherin:catenin complex, and stimulates cadherin mediated cell-cell adhesion. In this grant we now turn our focus to the role of integrins and cadherins in PKD, and in particular, how polycystins 1 and 2 may function in signal transduction pathways that affect integrin and cadherin function. Understanding the role of integrins and cadherins in PKD may eventually lead to pharmacological interventions that ameliorate cystogenesis. PKD is a cause of a significant portion of chronic renal failure that leads to dialysis and transplantation. This research aimed at understanding how PKD causes kidney damage, will yield information that should lead to treatments that help prevent kidney damage in PKD.