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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 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.

SUBMITTER: Ikeda T

PROVIDER: S-EPMC8484440 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Ikeda Takayuki T Yoshitake Yoshino Y Yoshitomi Yasuo Y Saito-Takatsuji Hidehito H Ishigaki Yasuhito Y Yonekura Hideto H

Scientific reports 20210930 1

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 cond ...[more]

PMID: 34593918

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

Publications

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

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