中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway

文献类型：期刊论文

作者You, Yan1,2,3; Bao, Wei-Lian2,3; Zhang, Su-Lin2,3; Li, Hai-Dong2,3; Li, Hui2,3; Dang, Wen-Zhen2,3; Zou, Si-Li5; Cao, Xin-Yue2,3; Wang, Xu2,3; Liu, Li-Xin2,3
刊名CIRCULATION RESEARCH
出版日期2020-07-31
卷号127期号:4页码:534-549
关键词atherosclerosis foam cell lipid metabolism monocytes sorting nexin
ISSN号0009-7330
DOI10.1161/CIRCRESAHA.119.315516
通讯作者Qu, Le-Feng(qulefeng@smmu.edu.cn) ; Zheng, Mingyue(myzheng@simm.ac.cn) ; Shen, Xiaoyan(shxiaoy@fudan.edu.cn)
英文摘要Rationale: SNX10 (sorting nexin 10) has been reported to play a critical role in regulating macrophage function and lipid metabolism. Objective: To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms. Methods and Results: SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE(-/-)(apolipoprotein E) background and atherogenesis (high-cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE(-/-)mice. Myeloid cell-specific SNX10 deficiency (Delta knockout [KO]) attenuated atherosclerosis progression in APOE(-/-)mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of Delta KO mice. In vitro experiments showed that SNX10 deficiency-inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT (protein kinase B). The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB (transcription factor EB), thereby enhanced lysosomal biogenesis and LAL (lysosomal acid lipase) activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype. Conclusions: Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.
WOS关键词CELL ; POLARIZATION ; ACTIVATION ; IMMUNOMETABOLISM ; DISRUPTION ; RESPONSES ; CD36 ; AXIS
资助项目National Natural Science Foundation of China[81773744] ; National Natural Science Foundation of China[81573441] ; National Natural Science Foundation of China[81971488] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020368] ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1903KF-05] ; Fudan-SIMM Joint Research Fund[FU-SIMM20183002]
WOS研究方向Cardiovascular System & Cardiology ; Hematology
语种英语
WOS记录号WOS:000559798700009
出版者LIPPINCOTT WILLIAMS & WILKINS
源URL[http://119.78.100.183/handle/2S10ELR8/292295]  
专题新药研究国家重点实验室
通讯作者Qu, Le-Feng; Zheng, Mingyue; Shen, Xiaoyan
作者单位1.Natl Inst Allergy & Infect, NIH, Rockville, MD USA
2.Fudan Univ, Dept Pharmacol, Sch Pharm, Minist Educ, Shanghai, Peoples R China
3.Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai, Peoples R China
4.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Beijing, Peoples R China
5.Second Mil Med Univ, Changzheng Hosp, Dept Vasc & Endovasc Surg, 415 Fengyang Rd, Shanghai 200003, Peoples R China
推荐引用方式
GB/T 7714		 You, Yan,Bao, Wei-Lian,Zhang, Su-Lin,et al. Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway[J]. CIRCULATION RESEARCH,2020,127(4):534-549.
APA You, Yan.,Bao, Wei-Lian.,Zhang, Su-Lin.,Li, Hai-Dong.,Li, Hui.,...&Shen, Xiaoyan.(2020).Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway.CIRCULATION RESEARCH,127(4),534-549.
MLA You, Yan,et al."Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway".CIRCULATION RESEARCH 127.4(2020):534-549.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。