Augmenter of liver regeneration protects the kidney against ischemia-reperfusion injury by inhibiting necroptosis.
Augmenter of liver regeneration protects the kidney against ischemia-reperfusion injury by inhibiting necroptosis.
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肝再生增强剂通过抑制坏死性凋亡保护肾脏免受缺血再灌注损伤
DOI：
10.1080/21655979.2022.2037248
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发表时间：
2022-03
期刊：
影响因子：
4.9
通讯作者：
Liao XH
中科院分区：
文献类型：
--
作者：
Liao YJ;Ma YX;Huang LL;Zhang Z;Tan FY;Deng LL;Cao D;Zeng XJ;Yu GQ;Liao XH
摘要 坏死性凋亡在急性肾损伤（AKI）的发病机制中发挥着重要作用，因此坏死性凋亡相关干预可能是治疗 AKI 的重要措施。我们前期的研究表明，肝再生增强剂（ALR）可以抑制肾小管上皮细胞凋亡并调节自噬；然而，ALR 对坏死性凋亡的影响仍不清楚。在本研究中，我们研究了ALR对缺血再灌注引起的坏死性凋亡的影响及其潜在机制。体内实验表明，肾脏特异性敲除ALR会加重缺血再灌注引起的肾功能障碍和病理损伤。同时，肾坏死性凋亡相关蛋白受体相互作用蛋白1（RIP1）、受体相互作用蛋白3（RIP3）和混合谱系激酶结构域样蛋白（MLKL）的表达显着增加。体外实验表明，ALR的过表达降低了缺氧-复氧诱导的肾损伤分子、炎症相关因子肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白的表达。此外，缺氧和复氧后升高的RIP1、RIP3和MLKL的表达也受到ALR过表达的抑制。体内和体外结果均表明ALR对缺血再灌注引起的急性肾损伤具有保护作用，RIP1/RIP3/MLKL通路作为可能的坏死性凋亡调节机制值得进一步验证。图文摘要
ABSTRACT Necroptosis plays an important role in the pathogenesis of acute kidney injury (AKI), and necroptosis-related interventions may therefore be an important measure for the treatment of AKI. Our previous study has shown that augmenter of liver regeneration (ALR) inhibits renal tubular epithelial cell apoptosis and regulates autophagy; however, the influence of ALR on necroptosis remains unclear. In this study, we investigated the effect of ALR on necroptosis caused by ischemia-reperfusion and the underlying mechanism. In vivo experiments indicated that kidney-specific knockout of ALR aggravated the renal dysfunction and pathological damage induced by ischemia-reperfusion. Simultaneously, the expression of renal necroptosis-associated protein receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and mixed-lineage kinase domain-like protein (MLKL) significantly increased. In vitro experiments indicated that overexpression of ALR decreased the expression of hypoxia-reoxygenation-induced kidney injury molecules, the inflammation-associated factor tumor necrosis factor-alpha (TNF-α), and monocyte chemotactic protein. Additionally, the expression of RIP1, RIP3, and MLKL, which are elevated after hypoxia and reoxygenation, was also inhibited by ALR overexpression. Both in vivo and in vitro results indicated that ALR has a protective effect against acute kidney injury caused by ischemia-reperfusion, and the RIP1/RIP3/MLKL pathway should be further verified as a probable necroptosis regulating mechanism. Graphical abstract
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DOI：
10.1186/1755-1536-5-10
发表时间：
2012-07-09
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Gandhi CR
通讯作者：
Gandhi CR
影响因子：
7.2
作者：
Huang, Li-li;Long, Rui-ting;Liao, Xiao-hui
通讯作者：
Liao, Xiao-hui
茯苓酸对肾缺血再灌注损伤铁死亡的影响及分子机制
影响因子：
3.4
作者：
Jiang, Gui-Ping;Liao, Yue-Juan;Liao, Xiao-Hui
通讯作者：
Liao, Xiao-Hui
影响因子：
10.5
作者：
Lin, Y;Devin, A;Liu, ZG
通讯作者：
Liu, ZG
RIP3 的裂解通过去除激酶结构域使其不依赖 caspase 的细胞凋亡途径失活
影响因子：
4.8
作者：
Feng, Shanshan;Yang, Yonghui;Wu, Mian
通讯作者：
Wu, Mian