干旱区生态环境知识资源中心(Arid): Desert hedgehog-primary cilia cross talk shapes mitral valve tissue by organizing smooth muscle actin

Arid

DOI	10.1016/j.ydbio.2020.03.003
	Desert hedgehog-primary cilia cross talk shapes mitral valve tissue by organizing smooth muscle actin
	Fulmer, Diana; Toomer, Katelynn A.; Glover, Janiece; Guo, Lilong; Moore, Kelsey; Moore, Reece; Stairley, Rebecca; Gensemer, Cortney; Abrol, Sameer; Rumph, Mary Kate; Emetu, Faith; Lipschutz, Joshua H.; McDowell, Colin; Bian, Justin; Wang, Christina; Beck, Tyler; Wessels, Andy; Renault, Marie-Ange; Norris, Russell A.
通讯作者	Norris, RA
来源期刊	DEVELOPMENTAL BIOLOGY
ISSN	0012-1606
EISSN	1095-564X
出版年	2020
卷号	463 期号:1 页码:26-38
英文摘要	Non-syndromic mitral valve prolapse (MVP) is the most common heart valve disease affecting 2.4% of the population. Recent studies have identified genetic defects in primary cilia as causative to MVP, although the mechanism of their action is currently unknown. Using a series of gene inactivation approaches, we define a paracrine mechanism by which endocardially-expressed Desert Hedgehog (DHH) activates primary cilia signaling on neighboring valve interstitial cells. High-resolution imaging and functional assays show that DHH de-represses smoothened at the primary cilia, resulting in kinase activation of RAC1 through the RAC1-GEF, TIAM1. Activation of this non-canonical hedgehog pathway stimulates alpha-smooth actin organization and ECM remodeling. Genetic or pharmacological perturbation of this pathway results in enlarged valves that progress to a myxomatous phenotype, similar to valves seen in MVP patients. These data identify a potential molecular origin for MVP as well as establish a paracrine DHH-primary cilium cross-talk mechanism that is likely applicable across developmental tissue types.
英文关键词	Primary cilia Desert hedgehog signaling Valve development Myxomatous degeneration
类型	Article
语种	英语
开放获取类型	Green Published, hybrid, Green Accepted
收录类别	SCI-E
WOS记录号	WOS:000536163200003
WOS关键词	ZINC-FINGER PROTEIN ; INTRAFLAGELLAR TRANSPORT ; SIGNAL-TRANSDUCTION ; AORTIC-VALVE ; PROLAPSE ; MUTATIONS ; FILAMIN ; DISEASE ; PATHWAYS ; MATRIX
WOS类目	Developmental Biology
WOS研究方向	Developmental Biology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/324567
作者单位	[Fulmer, Diana; Toomer, Katelynn A.; Glover, Janiece; Guo, Lilong; Moore, Kelsey; Moore, Reece; Stairley, Rebecca; Gensemer, Cortney; Abrol, Sameer; Rumph, Mary Kate; Emetu, Faith; McDowell, Colin; Bian, Justin; Wang, Christina; Beck, Tyler; Wessels, Andy; Norris, Russell A.] Med Univ South Carolina, Dept Regenerat Med & Cell Biol, 173 Ashley Ave,BSB 601, Charleston, SC 29425 USA; [Lipschutz, Joshua H.; Norris, Russell A.] Med Univ South Carolina, Dept Med, Charleston, SC 29425 USA; [Toomer, Katelynn A.] Johns Hopkins Univ, Dept Genet Med, Baltimore, MD USA; [Renault, Marie-Ange] Univ Bordeaux, INSERM, U1034, Pessac, France
推荐引用方式 GB/T 7714	Fulmer, Diana,Toomer, Katelynn A.,Glover, Janiece,et al. Desert hedgehog-primary cilia cross talk shapes mitral valve tissue by organizing smooth muscle actin[J],2020,463(1):26-38.
APA	Fulmer, Diana.,Toomer, Katelynn A..,Glover, Janiece.,Guo, Lilong.,Moore, Kelsey.,...&Norris, Russell A..(2020).Desert hedgehog-primary cilia cross talk shapes mitral valve tissue by organizing smooth muscle actin.DEVELOPMENTAL BIOLOGY,463(1),26-38.
MLA	Fulmer, Diana,et al."Desert hedgehog-primary cilia cross talk shapes mitral valve tissue by organizing smooth muscle actin".DEVELOPMENTAL BIOLOGY 463.1(2020):26-38.