GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway
文献类型：期刊论文
| 作者 | Li, Haidi2; Chen, Xin2; Xu, Jiejie2; Zhu, Lin2; Li, Chao2; Sun, Xiaolong2; Li, Xiaofeng2; Guo, Jianbo3; Li, Juanjuan2; Wang, Sheng2,6 |
| 刊名 | HEPATOLOGY
 |
| 出版日期 | 2023-07-05 |
| 页码 | 17 |
| ISSN号 | 0270-9139 |
| DOI | 10.1097/HEP.0000000000000531 |
| 通讯作者 | Meng, Xiao-ming(mengxiaoming@ahmu.edu.cn) ; Li, Jun(lj@ahmu.edu.cn) |
| 英文摘要 | Background and Aims: The common characteristics of alcohol-associated liver injury (ALI) include abnormal liver function, infiltration of inflammatory cells, and generation of oxidative stress. The gastrin-releasing peptide receptor (GRPR) is activated by its neuropeptide ligand, gastrin-releasing peptide (GRP). GRP/GRPR appears to induce the production of cytokines in immune cells and promotes neutrophil migration. However, the effects of GRP/GRPR in ALI are unknown. Approach and Results: We found high GRPR expression in the liver of patients with alcohol-associated steatohepatitis and increased pro-GRP levels in peripheral blood mononuclear cells of these patients compared with that of the control. Increased expression of GRP may be associated with histone H3 lysine 27 acetylation induced by alcohol, which promotes the expression of GRP and then GRPR binding. Grpr(-/-) and Grpr(flox/flox)LysM(Cre) mice alleviated ethanol-induced liver injury with relieved steatosis, lower serum alanine aminotransferase, aspartate aminotransferase, triglycerides, malondialdehyde, and superoxide dismutase levels, reduced neutrophil influx, and decreased expression and release of inflammatory cytokines and chemokines. Conversely, the overexpression of GRPR showed opposite effects. The pro-inflammatory and oxidative stress roles of GRPR might be dependent on IRF1-mediated Caspase-1 inflammasome and NOX2-dependent reactive oxygen species pathway, respectively. In addition, we verified the therapeutic and preventive effects of RH-1402, a novel GRPR antagonist, for ALI. Conclusions: A knockout or antagonist of GRPR during excess alcohol intake could have anti-inflammatory and antioxidative roles, as well as provide a platform for histone modification-based therapy for ALI. |
| WOS关键词 | GASTRIN-RELEASING-PEPTIDE ; RECEPTOR ANTAGONIST ; MODEL ; PATHOGENESIS ; ACETYLATION ; INHIBITION |
| 资助项目 | National Science Foundation of China[U19A2001] ; National Science Foundation of China[81970534] ; National Science Foundation of China[82070628] ; Research Fund of Anhui Institute of translational medicine[2021zhyx-B06] ; Major Projects of Science and Technology in Anhui Province[202103a07020013] ; University Synergy Innovation Program of Anhui Province[GXXT-2020-063] ; University Synergy Innovation Program of Anhui Province[GXXT-2020-025] |
| WOS研究方向 | Gastroenterology & Hepatology |
| 语种 | 英语 |
| 出版者 | LIPPINCOTT WILLIAMS & WILKINS |
| WOS记录号 | WOS:001137056600001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308645]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Meng, Xiao-ming; Li, Jun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Anhui Med Univ, Anhui Inst Innovat Drugs, Sch Pharm, Inflammat & Immune Mediated Dis Lab Anhui Prov, Hefei, Peoples R China 3.Univ Hong Kong, Sch Chinese Med, Hong Kong, Peoples R China 4.Anhui Med Univ, Sch Pharm, Hefei 230032, Peoples R China 5.Anhui Med Univ, Affiliated Hosp 1, Dept Oncol, Hefei, Peoples R China 6.Anhui Med Univ, Ctr Sci Res, Hefei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Haidi,Chen, Xin,Xu, Jiejie,et al. GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway[J]. HEPATOLOGY,2023:17. |
| APA | Li, Haidi.,Chen, Xin.,Xu, Jiejie.,Zhu, Lin.,Li, Chao.,...&Li, Jun.(2023).GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway.HEPATOLOGY,17. |
| MLA | Li, Haidi,et al."GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway".HEPATOLOGY (2023):17. |
入库方式： OAI收割
来源：上海药物研究所
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