南方科技大学知识苑(SUSTech KC): A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation

题名	A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation
作者	Guo, Ling1,2 ; Wang, Rong1,2 ; Zhang, Kuo1,2 ; Yuan, Jifan1,2 ; Wang, Jiaxin1,2 ; Wang, Xiaoxia 1,2; Ma, Jianfei 1,2; Wu, Chuanyue 3
通讯作者	Guo, Ling; Wu, Chuanyue
发表日期	2019-11
DOI	10.1083/jcb.201902022
发表期刊	JOURNAL OF CELL BIOLOGY 影响因子和分区
ISSN	0021-9525
EISSN	1540-8140
卷号	218 期号:11页码:3773-3794
摘要	Mechano-environment plays multiple critical roles in the control of mesenchymal stem cell (M5C) fate decision, but the underlying signaling mechanisms remain undefined. We report here a signaling axis consisting of PINCH-1, SMAD specific E3 ubiquitin protein ligase 1 (Smurf1), and bone morphogenetic protein type 2 receptor (BMPR2) that links mechano-environment to MSC fate decision. PINCH-1 interacts with Smurf1, which inhibits the latter from interacting with BMPR2 and consequently suppresses BMPR2 degradation, resulting in augmented BMP signaling and MSC osteogenic differentiation (OD). Extracellular matrix (ECM) stiffening increases PINCH-1 level and consequently activates this signaling axis. Depletion of PINCH-1 blocks stiff ECM-induced BMP signaling and OD, whereas overexpression of PINCH-1 overrides signals from soft ECM and promotes OD. Finally, perturbation of either Smurf1 or BMPR2 expression is sufficient to block the effects of PINCH-1 on BMP signaling and MSC fate decision. Our findings delineate a key signaling mechanism through which mechano-environment controls BMPR2 level and MSC fate decision.
相关链接	[来源记录]
收录类别	SCI
语种	英语
重要成果	NI期刊
学校署名	第一 ; 通讯
资助项目	Shenzhen Innovation Committee of Science and Technology grants[JCYJ20180302174228311] ; Shenzhen Innovation Committee of Science and Technology grants[ZDSYS20140509142721429]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000494843800020
出版者	ROCKEFELLER UNIV PRESS
ESI学科分类	MOLECULAR BIOLOGY & GENETICS
来源库	Web of Science
引用统计	被引频次[WOS]：13
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/44751
专题	南方科技大学医学院前沿与交叉科学研究院生命科学学院_生物系
作者单位	1.Southern Univ Sci & Technol, Acad Adv Interdisciplinary Studies, Shenzhen Key Lab Cell Microenvironm, Guangdong Prov Key Lab Cell Microenvironm & Dis R, Shenzhen, Peoples R China 2.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China 3.Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15260 USA
第一作者单位	南方科技大学医学院; 前沿与交叉科学研究院; 生物系
通讯作者单位	南方科技大学医学院; 前沿与交叉科学研究院; 生物系
第一作者的第一单位	南方科技大学医学院; 前沿与交叉科学研究院
推荐引用方式 GB/T 7714	Guo, Ling,Wang, Rong,Zhang, Kuo,et al. A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation[J]. JOURNAL OF CELL BIOLOGY,2019,218(11):3773-3794.
APA	Guo, Ling.,Wang, Rong.,Zhang, Kuo.,Yuan, Jifan.,Wang, Jiaxin.,...&Wu, Chuanyue.(2019).A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation.JOURNAL OF CELL BIOLOGY,218(11),3773-3794.
MLA	Guo, Ling,et al."A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation".JOURNAL OF CELL BIOLOGY 218.11(2019):3773-3794.