个人中心| | 帮助
高级检索
当前位置： 首页 > 详情页

Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis

| 认领 | 导出 | |

文献详情

资源类型：
WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Li Chao[1] * ; Ma Qiu-Ying[2] * ; Liu Xue-Qi[3] * ; Li Hai-di[1] * ; Yu Ming-Jun[4] ; Xie Shuai-Shuai[1] ; Ma Wen-Xian[1] ; Chen Ying[1] ; Wang Jia-Nan[1] ; He Ruo-Bing[1] ; Bian He-Ge[5] ; He Yuan[1] ; Gao Li[3] ; Deng Sheng-Song[4] ; Zang Hong-Mei[1] ; Gong Qian[6] ; Wen Jia-Gen[1] ; Liu Ming-Ming[1] ; Yang Chen[7] ; Chen Hai-Yong[8] ; Li Jun[1] ; Lan Hui-Yao[9] ; Jin Juan[5,*3] ; Yao Ri-Sheng[4,*2] ; Meng Xiao-Ming[1,*1] ;
机构： [1]Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China. [2]Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Public Health Clinical Center, No. 100 Huaihai Road, Hefei 230012, China. [3]Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. [4]School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China. [5]Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei 230032, China. [6]Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China. [7]Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Road, Zhanjiang 524001, China. [8]Department of Chinese Medicine, The University of Hong Kong-Shenzhen Hospital, The University of Hong Kong, Shenzhen 518009, China. [9]Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, and Liu Che Woo Institute of Innovative Medicine, Chinese University of Hong Kong, Shatin, Hong Kong 999077, China.
出处：
DOI： 10.1016/j.ymthe.2023.06.016
ISSN：

关键词： GRP GRPR STAT1 acute kidney injury inflammation necroptosis

摘要：
Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor [GRPR]) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

基金：
National Natural Science Foundation of China 615 (No. 81970584), the National Key R&D Program ( 2022YFC2502503), the Major Projects of Science and Technology in Anhui Province (202103a07020013), the Project of Collaborative Innovation for Colleges of Anhui Province (NO. GXXT-2021-070) and Scientific Research Fund of Anhui Medical University (NO.2019xkj057).
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 遗传学 1 区 生物工程与应用微生物 1 区 医学：研究与实验
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 生物工程与应用微生物 1 区 遗传学 1 区 医学：研究与实验
JCR分区：
出版当年[2021]版：
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China.
共同第一作者：
通讯作者：
通讯机构： [1]Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China. [4]School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China. [5]Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei 230032, China. [*1]School of Pharmacy, Anhui Medical University, Hefei, China [*2]School of Food and Biological Engineering,Hefei University of Technology, Hefei, China. [*3]Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University,Hefei, China.
推荐引用方式(GB/T 7714)：
Li Chao,Ma Qiu-Ying,Liu Xue-Qi,et al.Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis[J].MOLECULAR THERAPY.2023,31(9):2734-2754.doi:10.1016/j.ymthe.2023.06.016.
APA：
Li Chao,Ma Qiu-Ying,Liu Xue-Qi,Li Hai-di,Yu Ming-Jun...&Meng Xiao-Ming.(2023).Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis.MOLECULAR THERAPY,31,(9)
MLA：
Li Chao,et al."Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis".MOLECULAR THERAPY 31..9(2023):2734-2754

相关文献

[1]JianPiYiShen formula prevents cisplatin-induced acute kidney injury in mice by improving necroptosis through MAPK pathway [2]Gut-derived 4-hydroxyphenylacetic acid attenuates sepsis-induced acute kidney injury by upregulating ARC to inhibit necroptosis [3]Dihydroartemisinin attenuates lipopolysaccharide-induced acute kidney injury by inhibiting inflammation and oxidative stress. [4]A Chinese Medicine Compound Alleviates Cisplatin-Induced Acute Kidney Injury via Its Antiapoptosis and Anti-Inflammation Effects in Mice [5]The effect of monotropein on alleviating cisplatin-induced acute kidney injury by inhibiting oxidative damage, inflammation and apoptosis. [6]Neuropeptide Y protects kidney from acute kidney injury by inactivating M1 macrophages via the Y1R-NF-κB-Mincle-dependent mechanism [7]Huangqi-Danshen decoction protects against cisplatin-induced acute kidney injury in mice [8]Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway [9]Predicting in-hospital outcomes of patients with acute kidney injury [10]Research progress of astragaloside IV in treating acute kidney injury

资源点击量：2020 今日访问量：0 总访问量：646 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