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首页> 外文期刊>Journal of Cellular Physiology >Kidney Injury Molecule-1 Enhances Endocytosis of Albumin in Renal Proximal Tubular Cells
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Kidney Injury Molecule-1 Enhances Endocytosis of Albumin in Renal Proximal Tubular Cells

机译:肾损伤Molecule-1增强的内吞作用白蛋白在肾近端小管细胞

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Receptor-mediated endocytosis plays an important role in albumin reabsorption by renal proximal tubule epithelial cells. Kidney injury molecule-1 (KIM-1) is a scavenger receptor that is upregulated on the apical membrane of proximal tubules in proteinuric kidney disease. In this study, we examined the cellular localization and functional role of KIM-1 in cultured renal tubule epithelial cells (TECs). Confocal immunofluorescence microscopy reveals intracellular and cell surface localization of KIM-1 in primary renal TECs. Albumin stimulation resulted in a redistribution of KIM-1 and tight junction protein zonula occludens-1 in primary TEC monolayer. An increase in albumin internalization was observed in both primary TECs expressing endogenous KIM-1 and rat kidney cell line (NRK-52E) overexpressing exogenous KIM-1. KIM-1-induced albumin accumulation was abolished by its specific antibody. Moreover, endocytosed KIM-1 and its cargo proteins were delivered from endosomes to lysosomes for degradation in a clathrin-dependent pathway. Supportive evidence includes (1) detection of KIM-1 in Rab5-positive early endosomes, Rab7-positive late endosomes/multivesicular bodies, and LAMP1-positive lysosomes, (2) colocalization of KIM-1 and clathrin in the intracellular vesicles, and (3) blockade of KIM-1-mediated albumin internalization by chlorpromazine, an inhibitor of clathrin-dependent endocytosis. KIM-1 expression was upregulated by albumin but downregulated by transforming growth factor-beta 1. Taken together, our data indicate that KIM-1 increases albumin endocytosis in renal tubule epithelial cells, at least partially via a clathrin-dependent mechanism. (C) 2015 Wiley Periodicals, Inc.
机译:受体介导内吞作用中扮演一个重要的白蛋白的作用由肾脏近端再吸收小管上皮细胞。(KIM-1)是一个清道夫受体调节的顶端膜近端在proteinuric肾小管疾病。研究中,我们检测了细胞定位的KIM-1培养肾小管功能的作用上皮细胞(tec)。免疫荧光显微镜显示细胞内和细胞表面的本地化KIM-1原发性肾侦探。导致分配KIM-1和紧张结蛋白zonula occludens-1在初级TEC单层。内化是初级侦探观察表达内源性KIM-1和鼠肾细胞线(NRK-52E) overexpressing外生KIM-1。KIM-1-induced白蛋白积累被废除由其特定的抗体。KIM-1及其货物交付的蛋白质核内体中降解的溶酶体clathrin-dependent途径。包括(1)检测在Rab5-positive KIM-1早期核内体,Rab7-positive晚了核内体/多泡体,(2) colocalization LAMP1-positive溶酶体KIM-1和网格蛋白在细胞内的囊泡,和(3)KIM-1-mediated白蛋白的封锁氯丙嗪内化的抑制剂clathrin-dependent的内吞作用。表达式由白蛋白可调节通过转化生长因子表达下调1. 白蛋白增加肾小管的内吞作用上皮细胞,至少部分通过clathrin-dependent机制。期刊、公司。

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