机构：[1]Center for Metabolic Associated Fatty Liver Disease and Cholestatic Liver Diseases Center, Institute of Digestive Diseases of PLA, Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.[2]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.[3]Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, China.[4]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macau SAR, China.
LC3-associated phagocytosis (LAP) is an instrumental machinery for the clearance of extracellular particles including apoptotic cells for the alleviation of inflammation. While pharmacological approaches to modulate LAP for inflammation regulation have been poorly explored, in our study we identified a novel compound, columbamine (COL), which can trigger LAP and enhance efferocytosis in an animal model of colitis to attenuate inflammation. We found that COL directly binds to and biasedly activates FPR2 (formyl peptide receptor 2) to promote efferocytosis and alleviate colitis. Biochemically, COL induces an interaction between RAC1 and the PIK3C3/VPS34-RUBCN/RUBICON complex, stimulating LC3-associated efferocytosis. These findings provide a novel interpretation of the potential roles of LAP in regulating inflammatory bowel disease (IBD), reveal the relationship between G protein-coupled receptors (GPCRs) and LAP, and highlight the role of RAC1 in regulating the PIK3C3/VPS34-RUBCN complex in LAP.
基金：
Shenzhen Fundamental Research Program [No. SGDX20210823103804030], The Science and Technology Development Fund, Macau SAR [File no. 0025/2022/A1], The University of Macau grants [No. MYRG2022-00094-ICMS; MYRG-GRG2023- 00089-ICMS-UMDF], National Natural Science Foundation of China [No. 82271455], The Guangdong Basic and Applied Basic Research Foundation [No. 2022A1515012416], and The 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund [Guangdong-Hong Kong-Macau Joint Lab, No: 2020B1212030006] awarded to Jia-Hong Lu. This work is also partially supported by The Science Technology and Innovation Commission of Shenzhen Municipality (File no. GXWD20201231105722002-20200831175432002, JCYJ20200109150019113), and Joint Research Fund of the Second Affiliated Hospital-School of Medicine, The Chinese University of Hong Kong, Shenzhen awarded to Richard D. Ye and National Natural Science Foundation of China (No. 82200585) awarded to Ming-Yue Wu.
第一作者机构：[1]Center for Metabolic Associated Fatty Liver Disease and Cholestatic Liver Diseases Center, Institute of Digestive Diseases of PLA, Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, China.
共同第一作者：
通讯作者：
通讯机构：[2]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.[4]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macau SAR, China.
推荐引用方式(GB/T 7714)：
Wu Ming-Yue,Wang Er-Jin,Ye Richard D,et al.Enhancement of LC3-associated efferocytosis for the alleviation of intestinal inflammation[J].AUTOPHAGY.2024,1-2.doi:10.1080/15548627.2024.2311548.
APA：
Wu Ming-Yue,Wang Er-Jin,Ye Richard D&Lu Jia-Hong.(2024).Enhancement of LC3-associated efferocytosis for the alleviation of intestinal inflammation.AUTOPHAGY,,
MLA：
Wu Ming-Yue,et al."Enhancement of LC3-associated efferocytosis for the alleviation of intestinal inflammation".AUTOPHAGY .(2024):1-2
生物学