Anti-proteinuric effect of an endothelin-1 receptor antagonist in puromycin aminonucleoside induced nephrosis in rat.
Anti-proteinuric effect of an endothelin-1 receptor antagonist in puromycin aminonucleoside induced nephrosis in rat.
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内皮素-1 受体拮抗剂对嘌呤霉素氨基核苷诱导的大鼠肾病的抗蛋白尿作用。
DOI：
10.1038/pr.2018.11
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Kaneko K.
中科院分区：
文献类型：
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作者：
Kino J;Tsuji S;Kitao T;Akagawa Y;Yamanouchi S;Kimata T;Kaneko K.
背景特发性肾病综合征（INS）的发病机制仍不清楚，尽管最近的研究表明内皮素1（ET-1）和足细胞的CD80参与其中。我们通过抑制INS大鼠模型中的CD80来研究ET-1 A型受体（ETRA）拮抗剂作为治疗剂的潜力。方法将嘌呤霉素氨基核苷（PAN）注射给Wister大鼠以诱导蛋白尿：一些用ETRA拮抗剂治疗，另一些用0.5％甲基纤维素治疗。收集血液和组织样本。采用定量PCR检测肾脏中Toll样受体3（TLR-3）、核因子κB（NF-κB）、CD80、talin、ETRA和ET-1的表达。为了确定CD80蛋白表达水平，对肾组织进行免疫荧光染色和蛋白质印迹分析。结果治疗组蛋白尿量显着低于其他组。当日体重、血清肌酐值和血压没有显着差异。 ETRA 拮抗剂可恢复 PAN 损伤肾脏中足细胞足突的消失以及 TLR-3、核因子-κB (NF-κB) 和 CD80 的异常表达。结论 ETRA 拮抗剂可能是 INS 的有前途的药物，因为它具有抗蛋白尿作用。其作用被认为是通过抑制足细胞上的 CD80 表达而发挥作用。
BackgroundThe pathogenesis of idiopathic nephrotic syndrome (INS) remains unclear, although recent studies suggest endothelin 1 (ET-1) and CD80 of podocytes are involved. We investigated the potential of antagonist to ET-1 receptor type A (ETRA) as therapeutic agent through the suppression of CD80 in a rat model of INS.MethodsPuromycin aminonucleoside (PAN) was injected to Wister rats to induce proteinuria: some were treated with ETRA antagonist and others were treated with 0.5% methylcellulose. Blood and tissue samples were collected. Quantitative PCR was used to determine the expression of Toll-like receptor-3 (TLR-3), nuclear factor-κB (NF-κB), CD80, talin, ETRA, and ET-1 in the kidney. To confirm the level of CD80 protein expression, immunofluorescence staining and western blot analysis of the renal tissue were performed.ResultsAmount of proteinuria in the treatment group was significantly lower than the other groups. The same-day body weight, serum creatinine values, and blood pressure were not significantly different. ETRA antagonist restores podocyte foot process effacement as well as the aberrant expression of TLR-3, nuclear factor-κB (NF-κB), and CD80 in PAN-injured kidneys.ConclusionsThe ETRA antagonist may be promising drug for INS as it showed an antiproteinuric effect. Its action was considered to be through suppression of CD80 expression on podocytes.