VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers

Abstract Vascular endothelial growth factor A (VEGF-A) is a pivotal player in angiogenesis. It is capable of influencing such cellular processes as tubulogenesis and vascular smooth muscle cell (VSMC) proliferation, yet very little is known about the actual signaling events that mediate VEGF-A induc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xing Hua Liao, Yuan Xiang, Hui Li, De Liang Zheng, Yao Xu, Cheng Xi Yu, Jia Peng Li, Xiao Yu Zhang, Wei Bin Xing, Dong Sun Cao, Le Yuan Bao, Tong Cun Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1aab98069ba7455b9e2d642800d801ed
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1aab98069ba7455b9e2d642800d801ed
record_format	dspace
spelling	oai:doaj.org-article:1aab98069ba7455b9e2d642800d801ed2021-12-02T11:53:02ZVEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers10.1038/s41598-017-02907-62045-2322https://doaj.org/article/1aab98069ba7455b9e2d642800d801ed2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02907-6https://doaj.org/toc/2045-2322Abstract Vascular endothelial growth factor A (VEGF-A) is a pivotal player in angiogenesis. It is capable of influencing such cellular processes as tubulogenesis and vascular smooth muscle cell (VSMC) proliferation, yet very little is known about the actual signaling events that mediate VEGF-A induced VSMC phenotypic switch. In this report, we describe the identification of an intricate VEGF-A-induced signaling cascade that involves VEGFR2, STAT3, and Myocardin. We demonstrate that VEGF-A promotes VSMC proliferation via VEGFR2/STAT3-mediated upregulating the proliferation of markers like Cyclin D1 and PCNA. Specifically, VEGF-A leads to nitrosylation of Myocardin, weakens its effect on promoting the expression of contractile markers and is unable to inhibit the activation of STAT3. These observations reinforce the importance of nitric oxide and S-nitrosylation in angiogenesis and provide a mechanistic pathway for VEGF-A-induced VSMC phenotypic switch. In addition, Myocardin, GSNOR and GSNO can create a negative feedback loop to regulate the VSMC phenotypic switch. Thus, the discovery of this interactive network of signaling pathways provides novel and unexpected therapeutic targets for angiogenesis-dependent diseases.Xing Hua LiaoYuan XiangHui LiDe Liang ZhengYao XuCheng Xi YuJia Peng LiXiao Yu ZhangWei Bin XingDong Sun CaoLe Yuan BaoTong Cun ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xing Hua Liao Yuan Xiang Hui Li De Liang Zheng Yao Xu Cheng Xi Yu Jia Peng Li Xiao Yu Zhang Wei Bin Xing Dong Sun Cao Le Yuan Bao Tong Cun Zhang VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers
description	Abstract Vascular endothelial growth factor A (VEGF-A) is a pivotal player in angiogenesis. It is capable of influencing such cellular processes as tubulogenesis and vascular smooth muscle cell (VSMC) proliferation, yet very little is known about the actual signaling events that mediate VEGF-A induced VSMC phenotypic switch. In this report, we describe the identification of an intricate VEGF-A-induced signaling cascade that involves VEGFR2, STAT3, and Myocardin. We demonstrate that VEGF-A promotes VSMC proliferation via VEGFR2/STAT3-mediated upregulating the proliferation of markers like Cyclin D1 and PCNA. Specifically, VEGF-A leads to nitrosylation of Myocardin, weakens its effect on promoting the expression of contractile markers and is unable to inhibit the activation of STAT3. These observations reinforce the importance of nitric oxide and S-nitrosylation in angiogenesis and provide a mechanistic pathway for VEGF-A-induced VSMC phenotypic switch. In addition, Myocardin, GSNOR and GSNO can create a negative feedback loop to regulate the VSMC phenotypic switch. Thus, the discovery of this interactive network of signaling pathways provides novel and unexpected therapeutic targets for angiogenesis-dependent diseases.
format	article
author	Xing Hua Liao Yuan Xiang Hui Li De Liang Zheng Yao Xu Cheng Xi Yu Jia Peng Li Xiao Yu Zhang Wei Bin Xing Dong Sun Cao Le Yuan Bao Tong Cun Zhang
author_facet	Xing Hua Liao Yuan Xiang Hui Li De Liang Zheng Yao Xu Cheng Xi Yu Jia Peng Li Xiao Yu Zhang Wei Bin Xing Dong Sun Cao Le Yuan Bao Tong Cun Zhang
author_sort	Xing Hua Liao
title	VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers
title_short	VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers
title_full	VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers
title_fullStr	VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers
title_full_unstemmed	VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers
title_sort	vegf-a stimulates stat3 activity via nitrosylation of myocardin to regulate the expression of vascular smooth muscle cell differentiation markers
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1aab98069ba7455b9e2d642800d801ed
work_keys_str_mv	AT xinghualiao vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT yuanxiang vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT huili vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT deliangzheng vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT yaoxu vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT chengxiyu vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT jiapengli vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT xiaoyuzhang vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT weibinxing vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT dongsuncao vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT leyuanbao vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers AT tongcunzhang vegfastimulatesstat3activityvianitrosylationofmyocardintoregulatetheexpressionofvascularsmoothmusclecelldifferentiationmarkers
_version_	1718394910198988800

VEGF-A Stimulates STAT3 Activity via Nitrosylation of Myocardin to Regulate the Expression of Vascular Smooth Muscle Cell Differentiation Markers

Ejemplares similares