CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products
CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products
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DOI：
10.1152/ajprenal.00013.2008
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发表时间：
2008-12-01
影响因子：
4.2
通讯作者：
Otagiri, Masaki
中科院分区：
文献类型：
--
作者：
Iwao, Yasunori;Nakajou, Keisuke;Otagiri, Masaki
血浆晚期氧化蛋白产物（AOPP）的慢性蓄积可促进肾纤维化。然而，在细胞水平上的机制尚未阐明。在本研究中，人近端肾小管细胞（HK-2细胞）的内吞试验表明，AOPPs-人血清白蛋白（HSA）（氯胺修饰的HSA的体外制剂）显着内吞剂量依赖性的方式在一个更高的水平比HSA。免疫印迹分析证实HK-2细胞中B类清道夫受体的跨膜蛋白CD 36的表达。在使用在中国仓鼠卵巢（CHO）细胞中过表达人CD 36的细胞试验中，AOPPs-HSA被CD 36-CHO细胞显著内吞，但不被模拟CHO细胞内吞。此外，抗CD 36抗体处理可显著抑制HK-2细胞对AOPPs-HSA的内吞结合和降解，表明CD 36部分参与了HK-2细胞对AOPPs-HSA的摄取。AOPPs-HSA以剂量依赖性方式上调CD 36的表达。此外，AOPPs-HSA上调HK-2细胞中细胞内活性氧的产生和转化生长因子（TGF）-β 1的分泌，而抗CD 36抗体中和TGF-β 1的上调。这些结果表明AOPPs-HSA可能通过CD 36途径引起肾小管损伤。
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)-beta 1 in HK-2 cells, whereas anti-CD36 antibody neutralizes the upregulation of TGF-beta 1. These results suggest that AOPPs-HSA may cause renal tubular injury via the CD36 pathway.