EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells

Abstract Angiogenesis is physiologically essential for embryogenesis and development and reinitiated in adult animals during tissue growth and repair. Forming new vessels from the walls of existing vessels occurs as a multistep process coordinated by sprouting, branching, and a new lumenized network...

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Autores principales:	Takayuki Ikeda, Yoshino Yoshitake, Yasuo Yoshitomi, Hidehito Saito-Takatsuji, Yasuhito Ishigaki, Hideto Yonekura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1df7d47261f64904956c6d6b2c31091f
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spelling	oai:doaj.org-article:1df7d47261f64904956c6d6b2c31091f2021-12-02T17:17:40ZEPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells10.1038/s41598-021-98906-92045-2322https://doaj.org/article/1df7d47261f64904956c6d6b2c31091f2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98906-9https://doaj.org/toc/2045-2322Abstract Angiogenesis is physiologically essential for embryogenesis and development and reinitiated in adult animals during tissue growth and repair. Forming new vessels from the walls of existing vessels occurs as a multistep process coordinated by sprouting, branching, and a new lumenized network formation. However, little is known regarding the molecular mechanisms that form new tubular structures, especially molecules regulating the proper network density of newly formed capillaries. This study conducted microarray analyses in human primary microvascular endothelial cells (HMVECs) plated on Matrigel. The RAPGEF4 gene that encodes exchange proteins directly activated by cAMP 2 (EPAC2) proteins was increased in Matrigel-driven tubulogenesis. Tube formation was suppressed by the overexpression of EPAC2 and enhanced by EPAC2 knockdown in endothelial cells. Endothelial cell morphology was changed to round cell morphology by EPAC2 overexpression, while EPAC2 knockdown showed an elongated cell shape with filopodia-like protrusions. Furthermore, increased EPAC2 inhibited endothelial cell migration, and ablation of EPAC2 inversely enhanced cell mobility. These results suggest that EPAC2 affects the morphology and migration of microvascular endothelial cells and is involved in the termination and proper network formation of vascular tubes.Takayuki IkedaYoshino YoshitakeYasuo YoshitomiHidehito Saito-TakatsujiYasuhito IshigakiHideto YonekuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takayuki Ikeda Yoshino Yoshitake Yasuo Yoshitomi Hidehito Saito-Takatsuji Yasuhito Ishigaki Hideto Yonekura EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells
description	Abstract Angiogenesis is physiologically essential for embryogenesis and development and reinitiated in adult animals during tissue growth and repair. Forming new vessels from the walls of existing vessels occurs as a multistep process coordinated by sprouting, branching, and a new lumenized network formation. However, little is known regarding the molecular mechanisms that form new tubular structures, especially molecules regulating the proper network density of newly formed capillaries. This study conducted microarray analyses in human primary microvascular endothelial cells (HMVECs) plated on Matrigel. The RAPGEF4 gene that encodes exchange proteins directly activated by cAMP 2 (EPAC2) proteins was increased in Matrigel-driven tubulogenesis. Tube formation was suppressed by the overexpression of EPAC2 and enhanced by EPAC2 knockdown in endothelial cells. Endothelial cell morphology was changed to round cell morphology by EPAC2 overexpression, while EPAC2 knockdown showed an elongated cell shape with filopodia-like protrusions. Furthermore, increased EPAC2 inhibited endothelial cell migration, and ablation of EPAC2 inversely enhanced cell mobility. These results suggest that EPAC2 affects the morphology and migration of microvascular endothelial cells and is involved in the termination and proper network formation of vascular tubes.
format	article
author	Takayuki Ikeda Yoshino Yoshitake Yasuo Yoshitomi Hidehito Saito-Takatsuji Yasuhito Ishigaki Hideto Yonekura
author_facet	Takayuki Ikeda Yoshino Yoshitake Yasuo Yoshitomi Hidehito Saito-Takatsuji Yasuhito Ishigaki Hideto Yonekura
author_sort	Takayuki Ikeda
title	EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells
title_short	EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells
title_full	EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells
title_fullStr	EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells
title_full_unstemmed	EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells
title_sort	epac2 acts as a negative regulator in matrigel-driven tubulogenesis of human microvascular endothelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1df7d47261f64904956c6d6b2c31091f
work_keys_str_mv	AT takayukiikeda epac2actsasanegativeregulatorinmatrigeldriventubulogenesisofhumanmicrovascularendothelialcells AT yoshinoyoshitake epac2actsasanegativeregulatorinmatrigeldriventubulogenesisofhumanmicrovascularendothelialcells AT yasuoyoshitomi epac2actsasanegativeregulatorinmatrigeldriventubulogenesisofhumanmicrovascularendothelialcells AT hidehitosaitotakatsuji epac2actsasanegativeregulatorinmatrigeldriventubulogenesisofhumanmicrovascularendothelialcells AT yasuhitoishigaki epac2actsasanegativeregulatorinmatrigeldriventubulogenesisofhumanmicrovascularendothelialcells AT hidetoyonekura epac2actsasanegativeregulatorinmatrigeldriventubulogenesisofhumanmicrovascularendothelialcells
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EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells

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