Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis  

作　　者：Rui Xie Nan You Wan-Yan Chen Peng Zhu Pan Wang Yi-Pin Lv Geng-Yu Yue Xiao-Lin Xu Jiang-Bo Wu Jing-Yu Xu Si-Xu Liu Mu-Han Lü Sheng-Qian Yang Ping Cheng Fang-Yuan Mao Yong-Sheng Teng Liu-Sheng Peng Jin-Yu Zhang Ya-Ling Liao Shi-Ming Yang Yong-Liang Zhao Weisan Chen Quan-Ming Zou Yuan Zhuang 

机构地区：[1]Department ofEndoscopy and Digestive System,Guizhou Provincial People's Hospital,Guiyang,China [2]Department of Hepatobiliary Surgery,XinQiao Hospital,Third Military Medical University,Chongqing,China [3]National Engineering Research Center of Immunological Products,Department of Microbiology and Biochemical Pharmacy,College of Pharmacy and Laboratory Medicine,Third Military Medical University,Chongqing,China [4]Department of Gastroenterology,Suining First People's Hospital,Suining,Sichuan,China [5]Department of Infection,The General Hospital of Western Theater Command,Chengdu,Sichuan,China [6]Department of Gastroenterology,Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan,China [7]Chongqing Engineering Research Center for Pharmacodynamics Evaluation,Department of Pharmaceutics,College of Pharmacy and Laboratory Medicine,Third Military Medical University,Chongqing,China [8]Department of Gastroenterology,XinQiao Hospital,Third Military Medical University,Chongqing,China [9]Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery,Southwest Hospital,Third Military Medical University,Chongqing,China [10]La Trobe Institute of Molecular Science,La Trobe University,Bundoora,Victoria 3085,Australia [11]State Key Laboratory of Trauma and Chemical Poisoning,Chongqing,China

出　　处：《Research》2025年第1期718-738,共21页研究(英文)

基　　金：supported by grants of the National Natural Science Foundation of China(82000530,82071744,82070578,81870394,32160208,and 82170628);Outstanding Scientific Youth Fund of Guizhou Province(Qiankehe platform talents 2021-5647,Qiankehe platform talents GCC[2023]040);Key Projects of Guizhou Provincial Basic Research Program(Qiankehe foundation-ZK 2021-major project 004);Collaborative Innovation Center of Chinese Ministry of Education(2020-39);Joint project of Chongqing Health Commission and Science and Technology Bureau(2023MSXM004);Sichuan Science and Technology Program(2022ZYD0071);The General Hospital of Western Theater Command(2021-XZYG-B24).

摘　　要：Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa.Angiopoietin-like 4(ANGPTL4)is considered a double-edged sword in inflammation-associated diseases,but its function and clinical relevance in H.pylori-associated pathology are unknown.Here,we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H.pylori infection.Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells(GECs)synergistically induced by H.pylori and IL-17A in a cagA-dependent manner.Human gastric ANGPTL4 correlated with H.pylori colonization and the severity of gastritis,and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation.Importantly,H.pylori colonization and inflammation were attenuated in Il17a-/-,Angptl4-/-,and Il17a-/-Angptl4-/-mice.Mechanistically,ANGPTL4 bound to integrinαV(ITGAV)on GECs to suppress CXCL1 production by inhibiting ERK,leading to decreased gastric influx of neutrophils,thereby promoting H.pylori colonization;ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB,resulting in increased gastric influx of regulatory CD4+T cells(Tregs)via CCL5-CCR4-dependent migration.In turn,ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB,promoting H.pylori-associated gastritis.Overall,we propose a model in which ANGPTL4 collectively ensures H.pylori persistence and promotes gastritis.Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H.pylori infection.

关 键 词：gastric mucosaangiopoietin helicobacter pylori ANGIOPOIETIN infiltration mononuclear cells more COLONIZATION bacterial persistence chronic gastritis helicobacter pylori infection 

分 类 号：R573.3[医药卫生—消化系统]