Identification of the pathogenesis of nephrotic syndrome by analyses of signal transduction and proteome

裂隙隔膜是肾小球上皮细胞（足细胞）之间的细胞间连接，在肾小球超滤的选择性透过中起重要作用。为探讨小儿肾病综合征的特异性治疗方法，本研究从裂膈的结构和功能入手，探讨蛋白尿和肾病综合征的发病机制。我们揭示了（I）裂隙隔膜周转动力学在裂隙隔膜维持中的重要性，（II）裂隙隔膜的新组分，（III）裂隙隔膜信号传导的细胞内钙浓度机制，以及（IV）肾病患者足细胞功能蛋白表达的变化。我们的数据为遗传性和特发性肾病综合征中SD的形成和维持及其功能障碍提供了新的分子见解。

Slit diaphragm, an intercellular junction between renal glomerular epithelial cells (podocytes), is essential for the permselectivity in glomerular ultrafiltarion. To establish specific therapy for pediatric nephrotic syndrome, we focused on the structure and function of slit diaphragm (SD) and investigated the pathogenic mechanism of proteinuria and nephrotic syndrome. We revealed (I) the importance of dynamics of slit diaphragm turnover in the maintenance of slit diaphragm, (II) the novel component of slit diaphragm, (III) the mechanism of intracellular calcium concentration by slit diaphragm signaling, and (IV) the changes of expression of functional proteins in podocytes of nephrotic patients. Our data provide new molecular insights into the formation and maintenance of SD and its dysfunction in hereditary and idiopathic nephrotic syndrome.