CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products.
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)-beta1 in HK-2 cells, whereas anti-CD36 antibody neutralizes the upregulation of TGF-beta1. These results suggest that AOPPs-HSA may cause renal tubular injury via the CD36 pathway.
Iwao
Yasunori
Y
Dept. of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto Univ. 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Nakajou
Keisuke
K
Nagai
Ryoji
R
Kitamura
Kenichiro
K
Anraku
Makoto
M
Maruyama
Toru
T
Otagiri
Masaki
M
D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology; D007684:Kidney Tubules / Q000293:injuries*; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology
D018955:CD36 Antigens; D011506:Proteins; D017382:Reactive Oxygen Species; D012709:Serum Albumin