PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery

doi:10.1080/15548627.2020.1847799

	PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery
	Tang, Ying 3; Liu, Jinchang 1; Wang, Yu 3; Yang, Li 3; Han, Bing 3; Zhang, Yuan 3; Bai, Ying 3; Shen, Ling 3; Li, Mingyue 3; Jiang, Teng 1
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.