Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance

doi:10.1126/scitranslmed.aam8604

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance
	Yin, Lei-Miao 4; Xu, Yu-Dong 4; Peng, Ling-Ling 4; Duan, Ting-Ting 4; Liu, Jia-Yuan 4; Xu, Zhijian7 ; Wang, Wen-Qian 4; Guan, Nan 4; Han, Xiao-Jie 4; Li, Hai-Yan4
刊名	SCIENCE TRANSLATIONAL MEDICINE
	2018-02-07
卷号	10 期号:427
ISSN号	1946-6234
DOI	10.1126/scitranslmed.aam8604
文献子类	Article
英文摘要	There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than. 2-agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces pulmonary resistance in both ovalbumin-and house dust mite-induced asthma in mice. TSG12 induces RhoA phosphorylation, thereby inactivating the RhoA-ROCK-MYPT1-MLC pathway and causing ASMCs relaxation. TSG12 is more effective than. 2-agonists in relaxing human ASMCs and pulmonary resistance with potential clinical advantages. These results suggest that TSG12 could be a promising therapeutic approach for treating asthma.
资助项目	National Natural Science Foundation of China (NSFC)[81574058] ; National Natural Science Foundation of China (NSFC)[81473760] ; National Natural Science Foundation of China (NSFC)[81273435] ; Shanghai Talent Development Fund[201610] ; Shanghai Key Research Program of Shanghai Municipal Commission of Health and Family Planning[ZY3-CCCX-3-3005] ; NIH[R01-GM114180] ; Eastern Scholar[JZ2016010] ; NSFC[81774429]
WOS关键词	AIRWAY SMOOTH-MUSCLE ; ACTIN CYTOSKELETON ; TYROSINE KINASE ; ERM PROTEINS ; LUNG SLICES ; METALLOTHIONEIN ; CELLS ; DISEASE ; LIGHT ; RAT
WOS研究方向	Cell Biology ; Research & Experimental Medicine
语种	英语
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号	WOS:000424329400002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279911]
专题	药物发现与设计中心
通讯作者	Ulloa, Luis; Yang, Yong-Qing
作者单位	1.Georgia Regents Univ, Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA; 2.Shanghai Univ Tradit Chinese Med, Int Lab Neuroimmunomodulat, Shanghai 200030, Peoples R China; 3.Rutgers New Jersey Med Sch, Ctr Immunol & Inflammat, Newark, NJ 07101 USA 4.Shanghai Univ Tradit Chinese Med, Yueyang Hosp, Shanghai 200030, Peoples R China; 5.Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol, Shanghai 200025, Peoples R China; 6.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med, Shanghai 200030, Peoples R China; 7.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 8.Changzhou Univ, Inst Biomed Engn & Hlth Sci, Changzhou 213164, Jiangsu, Peoples R China;
推荐引用方式 GB/T 7714	Yin, Lei-Miao,Xu, Yu-Dong,Peng, Ling-Ling,et al. Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance[J]. SCIENCE TRANSLATIONAL MEDICINE,2018,10(427).
APA	Yin, Lei-Miao.,Xu, Yu-Dong.,Peng, Ling-Ling.,Duan, Ting-Ting.,Liu, Jia-Yuan.,...&Yang, Yong-Qing.(2018).Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance.SCIENCE TRANSLATIONAL MEDICINE,10(427).
MLA	Yin, Lei-Miao,et al."Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance".SCIENCE TRANSLATIONAL MEDICINE 10.427(2018).