Kidney injury molecule‐1 mediates endocytosis of albumin in renal proximal tubule (892.40)

Abstract

Kidney injury molecule‐1 (Kim‐1) is a scavenger receptor that is upregulated in proximal tubule epithelium in diabetic kidney disease. In this study, we examined the cellular location of Kim‐1 in proximal tubule cells and its role in renal handling of filtered protein. Immunostaining of primary mouse kidney tubular cells revealed that Kim‐1 was expressed in the plasma membrane and also prominent in the intracellular vesicles. An increase in binding and internalization of albumin was observed in both primary cultured tubular cells expressing endogenous Kim‐1 and the rat kidney cell line (NRK‐52E) overexpressing exogenous human Kim‐1. Kim‐1‐induced albumin accumulation was abolished by its specific antibody. Moreover, internalized proteins traffic through endosomes and are delivered to the lysosome for degradation in a clathrin‐dependent pathway. Supportive evidence includes a) detection of Kim‐1 in Rab5‐positive early endosomes, Rab7‐positive late endosomes/multivesicular bodies, and LAMP1‐positive lysosomes, b) colocalization of Kim‐1 and clathrin in the intracellular vesicles, and c) inhibition of Kim‐1‐mediated albumin uptake in the presence of chlorpromazine. In primary cultured tubular cells, the expression of Kim‐1 was significantly increased when exposed to elevated albumin concentration in culture medium. Taken together, our data indicate that Kim‐1 mediates albumin uptake in renal tubular epithelial cells, at least partly through a clathrin‐dependent mechanism. Kim‐1 may represent a potential therapeutic target in proteinuric nephropathy.Grant Funding Source: Supported by the NIH SDK096441 and NIH/NCRR/RCMI 5G12RR03034‐23