Resolvin D1 Induces mTOR-independent and ATG5-dependent Autophagy in BV-2 Microglial Cells  

作　　者：Shang-wen PAN Li-sha HU Han WANG Rui-ting LI Ya-jun HE You SHANG Zhong-liang DAI Li-xin CHEN Wei XIONG 

机构地区：[1]Department of Critical Care Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China [2]Department of Anesthesiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China [3]Department of Anesthesiology,Qingdao Women and Children’s Hospital,Qingdao University,Qingdao,266034,China [4]Department of Anesthesiology,The Second Clinical Medical College(Shenzhen People’s Hospital),Jinan University,Shenzhen,518020,China [5]Department of Pharmacology,Medical College,Jinan University,Guangzhou,510632,China [6]Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou,510632,China

出　　处：《Current Medical Science》2023年第6期1096-1106,共11页当代医学科学（英文）

基　　金：the National Natural Science Foundation of China(No.81902016).

摘　　要：Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.

关 键 词：resolvin D1 microglia mTOR-independent autophagy ATG5-dependent autophagy phagocytosis 

分 类 号：R614[医药卫生—麻醉学]