高级检索
当前位置: 首页 > 详情页

Gut-derived 4-hydroxyphenylacetic acid attenuates sepsis-induced acute kidney injury by upregulating ARC to inhibit necroptosis

文献详情

资源类型:
Pubmed体系:
机构: [1]Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China [3]Department of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, China [4]Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China [5]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
出处:
ISSN:

关键词: Sepsis 4-Hydroxyphenylacetic acid AKI ARC Necroptosis

摘要:
Studies have found that the plasma content of gut-derived 4-hydroxyphenylacetic acid (4-HPA) was significantly increased in septic patients. However, the mechanism of 4-HPA elevation during sepsis and its relationship with sepsis-induced acute kidney injury (SAKI) remain unclear.Cecal ligation and puncture (CLP) was performed in C57BL/6 mice to establish the SAKI animal model. Human renal tubular epithelial (HK-2) cells stimulated with lipopolysaccharide were used to establish the SAKI cell model. The widely targeted metabolomics was applied to analyze the renal metabolite changes after CLP. Proteomics was used to explore potential target proteins regulated by 4-HPA. The blood sample of clinical sepsis patients was collected to examine the 4-HPA content.We found that renal gut-derived 4-HPA levels were significantly increased after CLP. The high permeability of intestinal barrier after sepsis contributed to the dramatic increase of renal 4-HPA. Intriguingly, we demonstrated that exogenous 4-HPA administration could further significantly reduce CLP-induced increases in serum creatinine, urea nitrogen, and cystatin C, inhibit renal pathological damage and apoptosis, and improve the survival of mice. Mechanistically, 4-HPA inhibited necroptosis in renal tubular epithelial cells by upregulating the protein expression of apoptosis repressor with caspase recruitment domain (ARC) and enhancing the interaction between ARC and receptor-interacting protein kinase 1 (RIPK1).The increase of gut-derived 4-HPA in the kidney after sepsis could play a protective effect in SAKI by upregulating ARC to inhibit necroptosis.Copyright © 2023. Published by Elsevier B.V.

基金:
语种:
PubmedID:
中科院(CAS)分区:
出版当年[2022]版:
大类 | 2 区 生物学
小类 | 1 区 生物物理 2 区 生化与分子生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 生物物理 3 区 生化与分子生物学
第一作者:
第一作者机构: [1]Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
共同第一作者:
通讯作者:
通讯机构: [1]Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China [*1]Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:2022 今日访问量:0 总访问量:648 更新日期:2024-07-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 广东省中医院 技术支持:重庆聚合科技有限公司 地址:广州市越秀区大德路111号