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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/F1871    most recent 00013.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Iwao, Y. Articles by Otagiri, M. Search for Related Content PubMed PubMed Citation Articles by Iwao, Y. Articles by Otagiri, M.

CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products

¹Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, and Departments of ²Medical Biochemistry and ³Nephrology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

Submitted 10 January 2008 ; accepted in final form 23 October 2008

Chronic accumulation of plasma advanced oxidation protein products (AOPPs) promotes renal fibrosis. However, the mechanism at the cellular level has not been clarified. In the present study, endocytic assay of human proximal tubular cells (HK-2 cells) demonstrated that AOPPs-human serum albumin (HSA) (in vitro preparations of chloramine- modified HSA) were significantly endocytosed in a dose-dependent manner at a higher level than HSA. The expression of CD36, a transmembrane protein of the class B scavenger receptor, in HK-2 cells was confirmed in the immunoblot analysis. In a cellular assay using overexpressing human CD36 in Chinese hamster ovary (CHO) cells, AOPPs-HSA were significantly endocytosed by CD36-CHO cells but not by mock-CHO cells. Furthermore, the endocytic association and degradation of AOPPs-HSA by HK-2 cells was significantly inhibited by anti-CD36 antibody treatment, suggesting that CD36 is partly involved in the uptake of AOPPs-HSA by HK-2 cells. AOPPs-HSA upregulated the expression of CD36 in a dose-dependent manner. In addition, AOPPs-HSA upregulated the generation of intracellular reactive oxygen species and the secretion of transforming growth factor (TGF)-β1 in HK-2 cells, whereas anti-CD36 antibody neutralizes the upregulation of TGF-β1. These results suggest that AOPPs-HSA may cause renal tubular injury via the CD36 pathway.

endocytosis; transforming growth factor-β1