Indoxyl Sulfate Contributes to Adipose Tissue Inflammation through the Activation of NADPH Oxidase
Indoxyl Sulfate Contributes to Adipose Tissue Inflammation through the Activation of NADPH Oxidase
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硫酸吲哚酚通过激活NADPH氧化酶促进脂肪组织炎症
DOI：
10.3390/toxins12080502
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发表时间：
2020-08-01
期刊：
影响因子：
4.2
通讯作者：
Maruyama, Toru
中科院分区：
文献类型：
--
作者：
Tanaka, Shoma;Watanabe, Hiroshi;Maruyama, Toru
脂肪组织炎症似乎是慢性肾脏疾病（CKD）进展的一个危险因素，但CKD对脂肪组织炎症的影响尚不清楚。本研究的目的是阐明尿毒症毒素（吲哚硫酸酯（IS）、3-吲哚乙酸、对甲酰硫酸酯和犬尿酸）在ckd诱导的脂肪组织炎症中的作用。IS诱导分化的3T3L-1脂肪细胞单核细胞趋化蛋白-1 （MCP-1）表达和活性氧（ROS）产生。有机阴离子转运体（OAT）抑制剂、NADPH氧化酶抑制剂或抗氧化剂可抑制is诱导的MCP-1表达和ROS产生，提示OAT/NADPH氧化酶/ROS通路参与了is的作用。3T3L-1脂肪细胞与小鼠巨噬细胞共培养显示，培养的脂肪细胞巨噬细胞浸润增加。与未负荷的小鼠相比，健康小鼠的IS负荷增加了附睾脂肪组织中的IS水平、氧化应激和MCP-1表达。使用5/6肾切除小鼠，AST-120可抑制附睾脂肪组织氧化应激和MCP-1、F4/80和tnf - α的表达。这些集体数据表明IS可能是脂肪组织中ckd相关炎症反应的治疗靶点，AST-120可能有助于治疗IS诱导的脂肪组织炎症。
Adipose tissue inflammation appears to be a risk factor for the progression of chronic kidney disease (CKD), but the effect of CKD on adipose tissue inflammation is poorly understood. The purpose of this study was to clarify the involvement of uremic toxins (indoxyl sulfate (IS), 3-indoleacetic acid, p-cresyl sulfate and kynurenic acid) on CKD-induced adipose tissue inflammation. IS induces monocyte chemoattractant protein-1 (MCP-1) expression and reactive oxygen species (ROS) production in the differentiated 3T3L-1 adipocyte. An organic anion transporter (OAT) inhibitor, an NADPH oxidase inhibitor or an antioxidant suppresses the IS-induced MCP-1 expression and ROS production, suggesting the OAT/NADPH oxidase/ROS pathway is involved in the action of IS. Co-culturing 3T3L-1 adipocytes and mouse macrophage cells showed incubating adipocytes with IS increased macrophage infiltration. An IS-overload in healthy mice increased IS levels, oxidative stress and MCP-1 expression in epididymal adipose tissue compared to unloaded mice. Using 5/6-nephrectomized mice, the administration of AST-120 suppressed oxidative stress and the expression of MCP-1, F4/80 and TNF-alpha in epididymal adipose tissue. These collective data suggest IS could be a therapeutic target for the CKD-related inflammatory response in adipose tissue, and that AST-120 could be useful for the treatment of IS-induced adipose tissue inflammation.