PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery | |
Tang, Ying3; Liu, Jinchang1; Wang, Yu3; Yang, Li3; Han, Bing3; Zhang, Yuan3; Bai, Ying3; Shen, Ling3; Li, Mingyue3; Jiang, Teng1 | |
刊名 | AUTOPHAGY |
2021-10-03 | |
卷号 | 17期号:10页码:2905-2922 |
关键词 | Autophagy functional recovery ischemic stroke lysophosphatidic acid receptor 5 microglial activation poly (ADP-ribose) polymerase 14 |
ISSN号 | 1554-8627 |
DOI | 10.1080/15548627.2020.1847799 |
通讯作者 | Tang, Ying(tangying12345@126.com) ; Xu, Yungen(xyg@cpu.edu.cn) ; Yao, Honghong(yaohh@seu.edu.cn) |
英文摘要 | Stroke is a major public health problem leading to high rates of death and disability worldwide, but no effective pharmacological therapy is currently available except for the use of PLAT (plasminogen activator, tissue). Here we show that PARP14 (poly (ADP-ribose) polymerase family, member 14) level was significantly increased in the peri-infarct zone of photothrombotic stroke (PT) mice. Genetic knockdown and pharmacological inhibition of PARP14 aggravated functional impairment and increased infarct volume in PT mice, while overexpression of PARP14 displayed the opposite effects. Furthermore, PARP14 was abundant in microglia, and downregulation of PARP14 increased post-stroke microglial activation, whereas overexpression of PARP14 alleviated microglial activation, possibly through microglial macroautophagy/autophagy modulation. Mechanistically, overexpression of PARP14 suppressed Lpar5 (lysophosphatidic acid receptor 5) gene transcription to inhibit microglial activation post stroke. Taken together, PARP14 is a stroke-induced signal that restricts microglial activation and promotes functional recovery, and can serve as a novel target to develop new therapeutic agents for stroke. Moreover, these findings may be conducive to proper use of various PARP inhibitors. |
资助项目 | National Key Research and Development Program of China[2017YFA0104303] ; China Postdoctoral Science Foundation[2019M661700] ; Jiangsu Planned Projects for Postdoctoral Research Funds[2019K160] ; Natural Science Foundation of Jiangsu Province[BK20170593] ; National Natural Science Foundation of China[82003735] ; National Natural Science Foundation of China[81673410] ; National Natural Science Foundation of China[81761138048] ; National Natural Science Foundation of China[81973304] ; National Natural Science Foundation of China[81903591] ; National Science and Technology Major Project[ZX09201015] ; Jiangsu Innovation & Entrepreneurship Team Program, CAMS Innovation Fund for Medical Sciences (CIFMS)[2016-I2M-1-004] ; Fundamental Research Funds for the Central Universities[2242020K40128] ; Fundamental Research Funds for the Central Universities[2242019R20013] |
WOS研究方向 | Cell Biology |
语种 | 英语 |
出版者 | TAYLOR & FRANCIS INC |
WOS记录号 | WOS:000598593400001 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/298979] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Tang, Ying; Xu, Yungen; Yao, Honghong |
作者单位 | 1.China Pharmaceut Univ, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing, Peoples R China 2.Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Medica, State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China 3.Southeast Univ, Sch Med, Dept Pharmacol, Nanjing 210009, Jiangsu, Peoples R China 4.Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China 5.Southeast Univ, Key Lab Dev Genes & Human Dis, Inst Life Sci, Nanjing, Jiangsu, Peoples R China 6.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Jiangsu, Peoples R China |
推荐引用方式 GB/T 7714 | Tang, Ying,Liu, Jinchang,Wang, Yu,et al. PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery[J]. AUTOPHAGY,2021,17(10):2905-2922. |
APA | Tang, Ying.,Liu, Jinchang.,Wang, Yu.,Yang, Li.,Han, Bing.,...&Yao, Honghong.(2021).PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery.AUTOPHAGY,17(10),2905-2922. |
MLA | Tang, Ying,et al."PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery".AUTOPHAGY 17.10(2021):2905-2922. |
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