Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Pediatr Res. 2018 May;83(5):1041-1048. doi: 10.1038/pr.2018.11. Epub 2018 Feb 21.
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.
特发性肾病综合征（INS）的发病机制尚不清楚，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 大鼠模型中足细胞的 CD80 来研究内皮素 A 受体拮抗剂（ETRA）作为治疗剂的潜力。
用嘌呤霉素氨基核苷（PAN）注射 Wister 大鼠诱导蛋白尿：一部分用 ETRA 拮抗剂治疗，另一部分用 0.5%甲基纤维素治疗。采集血液和组织样本。采用定量 PCR 法测定肾组织中 Toll 样受体 3（TLR-3）、核因子-κB（NF-κB）、CD80、talin、ETRA 和 ET-1 的表达。为了确认 CD80 蛋白表达水平，对肾组织进行免疫荧光染色和 Western blot 分析。
治疗组的蛋白尿量明显低于其他组。同日体重、血清肌酐值和血压无明显差异。ETRA 拮抗剂可恢复足细胞足突融合，并纠正 PAN 损伤肾脏中 TLR-3、核因子-κB（NF-κB）和 CD80 的异常表达。
ETRA 拮抗剂可能是 INS 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。
