ACSL4 promotes microglia-mediated neuroinflammation by regulating lipid metabolism and VGLL4 expression

被引：60

作者：

Zhou, Xin ^{[1
,2
]}

Zhao, Rui ^{[3
]}

Lv, Mengfei ^{[1
,2
]}

Xu, Xiangyu ^{[1
,2
]}

Liu, Wenhao ^{[3
]}

Li, Xiaohua ^{[1
,2
]}

Gao, Yunyi ^{[1
,2
]}

Zhao, Zhiyuan ^{[3
]}

Zhang, Zhaolong ^{[3
]}

Li, Yuxuan ^{[2
]}

Xu, Rui ^{[3
]}

Wan, Qi ^{[1
,2
]}

Cui, Yu ^{[1
,2
]}

机构：

[1] Qingdao Univ, Inst Neuroregenerat & Neurorehabil, Ningxia Rd 308, Qingdao 266071, Shandong, Peoples R China

[2] Qingdao Univ, Qingdao Med Coll, Qingdao 266071, Peoples R China

[3] Qingdao Univ, Affiliated Hosp, Dept Intervent Radiol, Jiangsu Rd 16, Qingdao 266000, Shandong, Peoples R China

来源：

BRAIN BEHAVIOR AND IMMUNITY | 2023年 / 109卷

基金：

中国国家自然科学基金;

关键词：

ACSL4; Neuroinflammation; Microglia; LPS; PD; VGLL4; Lipid metabolism; DOPAMINERGIC NEURODEGENERATION; PARKINSONS-DISEASE; INNATE IMMUNITY; ISCHEMIC-STROKE; MODEL; INFLAMMATION; PHENOTYPES; RESPONSES; PROTECTS; MPTP;

D O I：

10.1016/j.bbi.2023.02.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme in polyunsaturated fatty acid (PUFA) metabolism. The role of ACSL4 in the lipopolysaccharide (LPS)-induced inflammation of microglia, and the effects of ACSL4-mediated inflammation on the progression of Parkinson's disease (PD) are unknown. In this study, we found that ACSL4 expression was increased after LPS stimulation. Knocking down ACSL4 in microglia decreased proinflammatory cytokine production. Mechanistically, ACSL4 reduced vestigial-like family member 4 (VGLL4) expression to promote NF-kappa B signal transduction; and ACSL4 regulated lipid composition after LPS stimulation. In addition, knocking down ACSL4 alleviated neuroinflammation in a systemic LPS model and acute l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) model. These data revealed ACSL4 to be a novel regulator that promotes microglia-mediated neuroinflammation by regulating VGLL4 expression and lipid metabolism.

引用

页码：331 / 343

页数：13

共 49 条

[1] TET2 Regulates the Neuroinflammatory Response in Microglia [J].

Carrillo-Jimenez, Alejandro ;

Deniz, Ozgen ;

Niklison-Chirou, Maria Victoria ;

Ruiz, Rocio ;

Bezerra-Salomao, Karina ;

Stratoulias, Vassilis ;

Amouroux, Rachel ;

Yip, Ping Kei ;

Vilalta, Anna ;

Cheray, Mathilde ;

Scott-Egerton, Alexander Michael ;

Rivas, Eloy ;

Tayara, Khadija ;

Garcia-Dominguez, Irene ;

Garcia-Revilla, Juan ;

Carlos Fernandez-Martin, Juan ;

Maria Espinosa-Oliva, Ana ;

Shen, Xianli ;

St George-Hyslop, Peter ;

Brown, Guy Charles ;

Hajkova, Petra ;

Joseph, Bertrand ;

Luis Venero, Jose ;

Branco, Miguel Ramos ;

Angel Burguillos, Miguel .

CELL REPORTS, 2019, 29 (03) :697-+

[2] ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway [J].

Chen, Junru ;

Ding, Chaofeng ;

Chen, Yunhao ;

Hu, Wendi ;

Yu, Chengkuan ;

Peng, Chuanhui ;

Feng, Xiaode ;

Cheng, Qiyang ;

Wu, Wenxuan ;

Lu, Yuejie ;

Xie, Haiyang ;

Zhou, Lin ;

Wu, Jian ;

Zheng, Shusen .

CANCER LETTERS, 2021, 502 :154-165

[3] ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation [J].

Cui, Yu ;

Zhang, Yan ;

Zhao, Xiaolong ;

Shao, Liming ;

Liu, Guoping ;

Sun, Chengjian ;

Xu, Rui ;

Zhang, Zhaolong .

BRAIN BEHAVIOR AND IMMUNITY, 2021, 93 :312-321

[4]

Deng XC, 2018, AM J CANCER RES, V8, P932

[5]

Doll S, 2017, NAT CHEM BIOL, V13, P91, DOI [10.1038/NCHEMBIO.2239, 10.1038/nchembio.2239]

[6] Role of Microglia in Neurological Disorders and Their Potentials as a Therapeutic Target [J].

Du, Li ;

Zhang, Ying ;

Chen, Yang ;

Zhu, Jie ;

Yang, Yi ;

Zhang, Hong-Liang .

MOLECULAR NEUROBIOLOGY, 2017, 54 (10) :7567-7584

[7] Dual function of VGLL4 in muscle regeneration [J].

Feng, Xue ;

Wang, Zuoyun ;

Wang, Fei ;

Lu, Tiantian ;

Xu, Jinjin ;

Ma, Xueyan ;

Li, Jinhui ;

He, Lingli ;

Zhang, Wenxiang ;

Li, Sheng ;

Yang, Wenjun ;

Zhang, Shu ;

Ge, Gaoxiang ;

Zhao, Yun ;

Hu, Ping ;

Zhang, Lei .

EMBO JOURNAL, 2019, 38 (17)

[8] The Role of Metabolic Enzymes in the Regulation of Inflammation [J].

Godfrey, Wesley H. ;

Kornberg, Michael D. .

METABOLITES, 2020, 10 (11) :1-22

[9] Protein kinase Cδ upregulation in microglia drives neuroinflammatory responses and dopaminergic neurodegeneration in experimental models of Parkinson's disease [J].

Gordon, Richard ;

Singh, Neeraj ;

Lawana, Vivek ;

Ghosh, Anamitra ;

Harischandra, Dilshan S. ;

Jin, Huajun ;

Hogan, Colleen ;

Sarkar, Souvarish ;

Rokad, Dharmin ;

Panicker, Nikhil ;

Anantharam, Vellareddy ;

Kanthasamy, Anumantha G. ;

Kanthasamy, Arthi .

NEUROBIOLOGY OF DISEASE, 2016, 93 :96-114

[10] ACSL4-dependent ferroptosis does not represent a tumor-suppressive mechanism but ACSL4 rather promotes liver cancer progression [J].

Grube, Julia ;

Woitok, Marius Maximilian ;

Mohs, Antje ;

Erschfeld, Stephanie ;

Lynen, Celina ;

Trautwein, Christian ;

Otto, Tobias .

CELL DEATH & DISEASE, 2022, 13 (08)

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