Apelin protects against acute renal injury by inhibiting TGF-β1
Apelin protects against acute renal injury by inhibiting TGF-β1
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Apelin 通过抑制 TGF-β 1 预防急性肾损伤
DOI：
10.1016/j.bbadis.2015.02.013
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发表时间：
2015-07-01
影响因子：
6.2
通讯作者：
Huang, Kun
中科院分区：
文献类型：
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作者：
Chen, Hong;Wan, Danyang;Huang, Kun
肾缺血/再灌注（I/R）损伤是急性肾损伤的最常见原因，具有高死亡率，并且目前没有有效的治疗方法。Apelin-13是一种具有生物活性的多肽，我们和其他人已经在几种小鼠模型中显示出对糖尿病肾病早期病变的抑制作用。为了测试爱帕琳-13是否保护免受肾I/R诱导的损伤，将雄性大鼠暴露于肾I/R损伤，用或不用爱帕琳-13治疗3天。爱帕琳-13治疗显著减少损伤诱导的肾小管病变、肾细胞凋亡，并使损伤诱导的肾功能障碍正常化。Apelin-13治疗可抑制损伤诱导的炎症因子和Tgf-β 1升高以及细胞凋亡。爱帕琳-13治疗还抑制肾I/R损伤后损伤诱导的组蛋白甲基化和Kmt 2d（H3 K4 me 2的组蛋白甲基转移酶）的升高。此外，在体外培养的肾小球系膜和肾小管细胞中，apelin-13抑制了在缺氧/再灌注（H/R）条件下损伤诱导的Tgf-β 1、凋亡、H3 K4 me 2和Kmt 2d的升高。Apelin过表达可显著抑制H/R诱导的TGF-β 1、细胞凋亡、H3 K4 me 2和Kmt 2d的升高。因此，本研究表明apelin-13可能是治疗急性肾损伤的治疗候选者。(C)2015 Elsevier B. V.版权所有。
Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury, having a high rate of mortality and no effective therapy currently available. Apelin-13, a bioactive peptide, has been shown to inhibit the early lesions of diabetic nephropathy in several mouse models by us and others. To test whether apelin-13 protects against renal I/R induced injury, male rats were exposed to renal I/R injury with or without apelin-13 treatment for 3 days. Apelin-13 treatment markedly reduced the injury-induced tubular lesions, renal cell apoptosis, and normalized the injury induced renal dysfunction. Apelin-13 treatment inhibited the injury-induced elevation of inflammatory factors and Tgf-beta 1, as well as apoptosis. Apelin-13 treatment also inhibited the injury-induced elevation of histone methylation and Kmt2d, a histone methyltransferase of H3K4me2, following renal I/R injury. Furthermore, in cultured renal mesangial and tubular cells, apelin-13 suppressed the injury-induced elevation of Tgf-beta 1, apoptosis, H3K4me2 and Kmt2d under the in vitro hypoxia/reperfusion (H/R) conditions. Consistently, over-expression of apelin significantly inhibited H/R-induced elevation of TGF-beta 1, apoptosis, H3K4me2 and Kmt2d. The present study therefore suggests apelin-13 may be a therapeutic candidate for treating acute kidney injury. (C) 2015 Elsevier B.V. All rights reserved.