Submitted on January 10, 2008
Accepted on October 23, 2008
CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products
Yasunori Iwao1, Keisuke Nakajou1, Ryoji Nagai2, Kenichiro Kitamura3, Makoto Anraku1, Toru Maruyama1, and Masaki Otagiri4*
1 Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 862-0973, Japan
2 Department of Medical Biochemistry, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 860-8556, Japan
3 Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 860-8556, Japan
4 Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
* To whom correspondence should be addressed. E-mail: otagirim{at}gpo.kumamoto-u.ac.jp.
Chronic accumulation of plasma advanced oxidation protein products (AOPPs) promotes renal fibrosis. However, the mechanism at cellular level has not been clarified. In the present study, endocytic assay of human proximal tubular cells (HK-2 cells) demonstrated that AOPPs-HSA (in vitro preparations of chloramine-T modified human serum albumin (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 over-expressing human CD36 in 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 TGF-
1 in HK-2 cells, whereas anti-CD36 antibody neutralize the upregulation of TGF-1. These results suggest that AOPPs-HSA may cause renal tubular injury via the CD36 pathway.
