ELABELA and an ELABELA Fragment Protect against AKI
ELABELA and an ELABELA Fragment Protect against AKI
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ELABELA 和 ELABELA 片段可预防 AKI
DOI：
10.1681/asn.2016111210
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发表时间：
2017-09-01
影响因子：
13.6
通讯作者：
Huang, Kun
中科院分区：
文献类型：
--
作者：
Chen, Hong;Wang, Lin;Huang, Kun
肾缺血再灌注（I/R）损伤是阿基最常见的原因，与高死亡率相关，目前尚无有效的治疗方法。ELABELA（ELA）是一种新发现的在成人肾脏中高表达的32个氨基酸残基的激素肽。为了研究ELA是否对肾I/R损伤具有保护作用，我们在体外将成熟肽（ELA 32）或11个残基的弗林蛋白酶切割片段（ELA 11）给予缺氧再灌注（H/R）损伤或阿霉素处理的肾小管细胞。ELA 32和ELA 11显著抑制H/R损伤的肾小管细胞的DNA损伤反应、凋亡和炎症的升高，并抑制阿霉素诱导的DNA损伤反应。类似地，ELA 32或ELA 11的过表达显著抑制H/R诱导的细胞死亡、DNA损伤反应和炎症。值得注意的是，用ELA 32或ELA 11而不是在N末端半胱氨酸被丙氨酸取代的ELA 11突变体（AE 11 C）治疗小鼠抑制了I/R损伤诱导的肾纤维化、炎症、凋亡和DNA损伤反应，并显著减少了肾小管病变和肾功能障碍。总之，我们的研究结果表明，ELA 32和ELA 11可能是治疗阿基的治疗候选者。
Renal ischemia-reperfusion (I/R) injury is the most common cause of AKI, which associates with high mortality and has no effective therapy. ELABELA (ELA) is a newly identified 32-residue hormone peptide highly expressed in adult kidney. To investigate whether ELA has protective effects on renal I/R injury, we administered the mature peptide (ELA32) or the 11-residue furin-cleaved fragment (ELA11) to hypoxia-reperfusion (H/R)-injured or adriamycin-treated renal tubular cells in vitro. ELA32 and ELA11 significantly inhibited the elevation of the DNA damage response, apoptosis, and inflammation in H/R-injured renal tubular cells and suppressed adriamycin-induced DNA damage response. Similarly, overexpression of ELA32 or ELA11 significantly inhibited H/R-induced cell death, DNA damage response, and inflammation. Notably, treatment of mice with ELA32 or ELA11 but not an ELA11 mutant with a cysteine to alanine substitution at the N terminus (AE11C) inhibited I/R injury-induced renal fibrosis, inflammation, apoptosis, and the DNA damage response and markedly reduced the renal tubular lesions and renal dysfunction. Together, our results suggest that ELA32 and ELA11 may be therapeutic candidates for treating AKI.