Endothelial RhoA GTPase is essential for in vitro endothelial functions but dispensable for physiological in vivo angiogenesis

Fatema Tuz Zahra, Md Sanaullah Sajib, Yusuke Ichiyama, Racheal Grace Akwii, Paul E. Tullar, Christopher Cobos, Shelby A. Minchew, Colleen L. Doçi, Yi Zheng, Yoshiaki Kubota, J. Silvio Gutkind, Constantinos M. Mikelis

Research output: Contribution to journalArticle

Abstract

Imbalanced angiogenesis is a characteristic of several diseases. Rho GTPases regulate multiple cellular processes, such as cytoskeletal rearrangement, cell movement, microtubule dynamics, signal transduction and gene expression. Among the Rho GTPases, RhoA, Rac1 and Cdc42 are best characterized. The role of endothelial Rac1 and Cdc42 in embryonic development and retinal angiogenesis has been studied, however the role of endothelial RhoA is yet to be explored. Here, we aimed to identify the role of endothelial RhoA in endothelial cell functions, in embryonic and retinal development and explored compensatory mechanisms. In vitro, RhoA is involved in cell proliferation, migration and tube formation, triggered by the angiogenesis inducers Vascular Endothelial Growth Factor (VEGF) and Sphingosine-1 Phosphate (S1P). In vivo, through constitutive and inducible endothelial RhoA deficiency we tested the role of endothelial RhoA in embryonic development and retinal angiogenesis. Constitutive endothelial RhoA deficiency, although decreased survival, was not detrimental for embryonic development, while inducible endothelial RhoA deficiency presented only mild deficiencies in the retina. The redundant role of RhoA in vivo can be attributed to potential differences in the signaling cues regulating angiogenesis in physiological versus pathological conditions and to the alternative compensatory mechanisms that may be present in the in vivo setting.

Original languageEnglish
Article number11666
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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GTP Phosphohydrolases
Embryonic Development
rho GTP-Binding Proteins
Cell Movement
Physiologic Neovascularization
Angiogenesis Inducing Agents
Microtubules
Vascular Endothelial Growth Factor A
Cues
Retina
Signal Transduction
Endothelial Cells
Cell Proliferation
Gene Expression
In Vitro Techniques

ASJC Scopus subject areas

  • General

Cite this

Zahra, F. T., Sajib, M. S., Ichiyama, Y., Akwii, R. G., Tullar, P. E., Cobos, C., ... Mikelis, C. M. (2019). Endothelial RhoA GTPase is essential for in vitro endothelial functions but dispensable for physiological in vivo angiogenesis. Scientific reports, 9(1), [11666]. https://doi.org/10.1038/s41598-019-48053-z

Endothelial RhoA GTPase is essential for in vitro endothelial functions but dispensable for physiological in vivo angiogenesis. / Zahra, Fatema Tuz; Sajib, Md Sanaullah; Ichiyama, Yusuke; Akwii, Racheal Grace; Tullar, Paul E.; Cobos, Christopher; Minchew, Shelby A.; Doçi, Colleen L.; Zheng, Yi; Kubota, Yoshiaki; Gutkind, J. Silvio; Mikelis, Constantinos M.

In: Scientific reports, Vol. 9, No. 1, 11666, 01.12.2019.

Research output: Contribution to journalArticle

Zahra, FT, Sajib, MS, Ichiyama, Y, Akwii, RG, Tullar, PE, Cobos, C, Minchew, SA, Doçi, CL, Zheng, Y, Kubota, Y, Gutkind, JS & Mikelis, CM 2019, 'Endothelial RhoA GTPase is essential for in vitro endothelial functions but dispensable for physiological in vivo angiogenesis', Scientific reports, vol. 9, no. 1, 11666. https://doi.org/10.1038/s41598-019-48053-z
Zahra, Fatema Tuz ; Sajib, Md Sanaullah ; Ichiyama, Yusuke ; Akwii, Racheal Grace ; Tullar, Paul E. ; Cobos, Christopher ; Minchew, Shelby A. ; Doçi, Colleen L. ; Zheng, Yi ; Kubota, Yoshiaki ; Gutkind, J. Silvio ; Mikelis, Constantinos M. / Endothelial RhoA GTPase is essential for in vitro endothelial functions but dispensable for physiological in vivo angiogenesis. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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