长期饮酒会通过整合素β1/JNK信号转导加重急性肾损伤。

IF 10.7 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Redox Biology Pub Date : 2024-10-03 DOI:10.1016/j.redox.2024.103386
Zhanji Zhan , Jiongcheng Chen , Hong Zhou , Xue Hong , Li Li , Xianhui Qin , Haiyan Fu , Youhua Liu
{"title":"长期饮酒会通过整合素β1/JNK信号转导加重急性肾损伤。","authors":"Zhanji Zhan ,&nbsp;Jiongcheng Chen ,&nbsp;Hong Zhou ,&nbsp;Xue Hong ,&nbsp;Li Li ,&nbsp;Xianhui Qin ,&nbsp;Haiyan Fu ,&nbsp;Youhua Liu","doi":"10.1016/j.redox.2024.103386","DOIUrl":null,"url":null,"abstract":"<div><div>Alcohol abuse is one of the major public health problems in the world and is associated with various health conditions. However, little is known about the effect of alcohol consumption on acute kidney injury (AKI). In this study, we demonstrate that chronic and binge alcohol feeding with a Lieber-DeCarli diet containing 5 % ethanol for 10 days, followed by a single dose of 31.5 % ethanol by gavage, aggravated AKI after ischemia-reperfusion injury (IRI) in female, but not in male, mice. Kidney dysfunction, histopathology and tubular cell apoptosis were more severe in EtOH-fed female mice after IRI, compared to pair-fed controls. RNA sequencing and experimental validation uncovered that activation of integrin β1 and its downstream c-Jun NH2-terminal kinase (JNK) aggravated AKI in EtOH-fed mice. Knockdown of integrin β1 inhibited JNK phosphorylation and alleviated AKI in EtOH-fed mice, whereas activation of integrin β1 by agonist antibody increased JNK phosphorylation, worsened renal histological injury and tubular cell apoptosis, and aggravated kidney dysfunction. In vitro, activation of integrin β1 increased JNK phosphorylation and induced tubular epithelial cell apoptosis. The detrimental effect of EtOH feeding was primarily mediated by acetaldehyde, as its levels were increased in the blood, liver and kidney of female mice fed with ethanol. Acetaldehyde per se activated integrin β1/JNK signaling and induced tubular cell apoptosis <em>in vitro</em>. These findings suggest that alcohol consumption increases vulnerability to AKI in female mice, which is probably mediated by acetaldehyde/integrin β1/JNK signaling cascade.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103386"},"PeriodicalIF":10.7000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chronic alcohol consumption aggravates acute kidney injury through integrin β1/JNK signaling\",\"authors\":\"Zhanji Zhan ,&nbsp;Jiongcheng Chen ,&nbsp;Hong Zhou ,&nbsp;Xue Hong ,&nbsp;Li Li ,&nbsp;Xianhui Qin ,&nbsp;Haiyan Fu ,&nbsp;Youhua Liu\",\"doi\":\"10.1016/j.redox.2024.103386\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Alcohol abuse is one of the major public health problems in the world and is associated with various health conditions. However, little is known about the effect of alcohol consumption on acute kidney injury (AKI). In this study, we demonstrate that chronic and binge alcohol feeding with a Lieber-DeCarli diet containing 5 % ethanol for 10 days, followed by a single dose of 31.5 % ethanol by gavage, aggravated AKI after ischemia-reperfusion injury (IRI) in female, but not in male, mice. Kidney dysfunction, histopathology and tubular cell apoptosis were more severe in EtOH-fed female mice after IRI, compared to pair-fed controls. RNA sequencing and experimental validation uncovered that activation of integrin β1 and its downstream c-Jun NH2-terminal kinase (JNK) aggravated AKI in EtOH-fed mice. Knockdown of integrin β1 inhibited JNK phosphorylation and alleviated AKI in EtOH-fed mice, whereas activation of integrin β1 by agonist antibody increased JNK phosphorylation, worsened renal histological injury and tubular cell apoptosis, and aggravated kidney dysfunction. In vitro, activation of integrin β1 increased JNK phosphorylation and induced tubular epithelial cell apoptosis. The detrimental effect of EtOH feeding was primarily mediated by acetaldehyde, as its levels were increased in the blood, liver and kidney of female mice fed with ethanol. Acetaldehyde per se activated integrin β1/JNK signaling and induced tubular cell apoptosis <em>in vitro</em>. These findings suggest that alcohol consumption increases vulnerability to AKI in female mice, which is probably mediated by acetaldehyde/integrin β1/JNK signaling cascade.</div></div>\",\"PeriodicalId\":20998,\"journal\":{\"name\":\"Redox Biology\",\"volume\":\"77 \",\"pages\":\"Article 103386\"},\"PeriodicalIF\":10.7000,\"publicationDate\":\"2024-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Redox Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213231724003641\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213231724003641","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

酗酒是世界上主要的公共卫生问题之一,与各种健康状况有关。然而,人们对饮酒对急性肾损伤(AKI)的影响知之甚少。在这项研究中,我们证明了用含 5% 乙醇的 Lieber-DeCarli 饮料连续 10 天喂养雌性小鼠(而不是雄性小鼠)慢性和暴饮暴食酒精,然后单剂量灌胃 31.5% 的乙醇,会加重小鼠缺血再灌注损伤(IRI)后的急性肾损伤(AKI)。与对饲对照组相比,饲喂乙醇的雌性小鼠在缺血再灌注损伤后的肾功能障碍、组织病理学和肾小管细胞凋亡更为严重。RNA测序和实验验证发现,整合素β1及其下游的c-Jun NH2-末端激酶(JNK)的激活加重了EtOH喂养小鼠的AKI。敲除整合素β1可抑制JNK磷酸化并缓解EtOH喂养小鼠的AKI,而通过激动剂抗体激活整合素β1可增加JNK磷酸化,加重肾组织学损伤和肾小管细胞凋亡,并加剧肾功能障碍。在体外,激活整合素β1会增加JNK磷酸化,诱导肾小管上皮细胞凋亡。喂食乙醇的有害影响主要由乙醛介导,因为乙醛在喂食乙醇的雌性小鼠的血液、肝脏和肾脏中含量增加。乙醛本身会激活整合素β1/JNK信号传导,诱导体外肾小管细胞凋亡。这些发现表明,饮酒会增加雌性小鼠对 AKI 的易感性,这可能是由乙醛/整合素 β1/JNK 信号级联介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Chronic alcohol consumption aggravates acute kidney injury through integrin β1/JNK signaling
Alcohol abuse is one of the major public health problems in the world and is associated with various health conditions. However, little is known about the effect of alcohol consumption on acute kidney injury (AKI). In this study, we demonstrate that chronic and binge alcohol feeding with a Lieber-DeCarli diet containing 5 % ethanol for 10 days, followed by a single dose of 31.5 % ethanol by gavage, aggravated AKI after ischemia-reperfusion injury (IRI) in female, but not in male, mice. Kidney dysfunction, histopathology and tubular cell apoptosis were more severe in EtOH-fed female mice after IRI, compared to pair-fed controls. RNA sequencing and experimental validation uncovered that activation of integrin β1 and its downstream c-Jun NH2-terminal kinase (JNK) aggravated AKI in EtOH-fed mice. Knockdown of integrin β1 inhibited JNK phosphorylation and alleviated AKI in EtOH-fed mice, whereas activation of integrin β1 by agonist antibody increased JNK phosphorylation, worsened renal histological injury and tubular cell apoptosis, and aggravated kidney dysfunction. In vitro, activation of integrin β1 increased JNK phosphorylation and induced tubular epithelial cell apoptosis. The detrimental effect of EtOH feeding was primarily mediated by acetaldehyde, as its levels were increased in the blood, liver and kidney of female mice fed with ethanol. Acetaldehyde per se activated integrin β1/JNK signaling and induced tubular cell apoptosis in vitro. These findings suggest that alcohol consumption increases vulnerability to AKI in female mice, which is probably mediated by acetaldehyde/integrin β1/JNK signaling cascade.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Redox Biology
Redox Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
19.90
自引率
3.50%
发文量
318
审稿时长
25 days
期刊介绍: Redox Biology is the official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe. It is also affiliated with the International Society for Free Radical Research (SFRRI). This journal serves as a platform for publishing pioneering research, innovative methods, and comprehensive review articles in the field of redox biology, encompassing both health and disease. Redox Biology welcomes various forms of contributions, including research articles (short or full communications), methods, mini-reviews, and commentaries. Through its diverse range of published content, Redox Biology aims to foster advancements and insights in the understanding of redox biology and its implications.
期刊最新文献
Bariatric surgery blunts nitrate-mediated improvements in cardiovascular function of overweight women by interfering with gastric S-nitrosothiol formation Corrigendum to "FBXL4 protects against HFpEF through Drp1-Mediated regulation of mitochondrial dynamics and the downstream SERCA2a" [Redox Biol. 70 (2024) 103081]. Corrigendum to "Shank3 ameliorates neuronal injury after cerebral ischemia/reperfusion via inhibiting oxidative stress and inflammation" [Redox Biol. 69 (2024) 102983]. Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation Corrigendum to "Complement receptor 3 mediates NADPH oxidase activation and dopaminergic neurodegeneration through a Src-Erk-dependent pathway" [Redox Biol. 14 (2018) 250-260].
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1