Work

Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis

Public Deposited

MLA citation style (9th ed.)

Mikelis, C, et al. Angiopoietin-2-induced Lymphatic Endothelial Cell Migration Drives Lymphangiogenesis Via the Β1 Integrin-rhoa-formin Axis. Springer Nature. 2022. mushare.marian.edu/concern/generic_works/b5e90093-be1e-470f-b1df-a94efd4315b6?locale=en.

APA citation style (7th ed.)

M. C, Z. Y, Z. F, G. J, Z. M, A. R, D. C. L, T. P, & S. S. (2022). Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis. https://mushare.marian.edu/concern/generic_works/b5e90093-be1e-470f-b1df-a94efd4315b6?locale=en

Chicago citation style (CMOS 17, author-date)

Mikelis, C., Zheng, Y., Zahra, F., Gutkind, J., Zabet-Moghaddam, M., Akwii, R., Doci, Colleen L. et al. Angiopoietin-2-Induced Lymphatic Endothelial Cell Migration Drives Lymphangiogenesis Via the Β1 Integrin-Rhoa-Formin Axis. Springer Nature. 2022. https://mushare.marian.edu/concern/generic_works/b5e90093-be1e-470f-b1df-a94efd4315b6?locale=en.

Note: These citations are programmatically generated and may be incomplete.

Lymphangiogenesis is an essential physiological process but also a determining factor in vascular-related pathological conditions. Angiopoietin-2 (Ang2) plays an important role in lymphatic vascular development and function and its upregulation has been reported in several vascular-related diseases, including cancer. Given the established role of the small GTPase RhoA on cytoskeleton-dependent endothelial functions, we investigated the relationship between RhoA and Ang2-induced cellular activities. This study shows that Ang2-driven human dermal lymphatic endothelial cell migration depends on RhoA. We demonstrate that Ang2-induced migration is independent of the Tie receptors, but dependent on β1 integrin-mediated RhoA activation with knockdown, pharmacological approaches, and protein sequencing experiments. Although the key proteins downstream of RhoA, Rho kinase (ROCK) and myosin light chain, were activated, blockade of ROCK did not abrogate the Ang2-driven migratory effect. However, formins, an alternative target of RhoA, were identified as key players, and especially FHOD1. The Ang2-RhoA relationship was explored in vivo, where lymphatic endothelial RhoA deficiency blocked Ang2-induced lymphangiogenesis, highlighting RhoA as an important target for anti-lymphangiogenic treatments.

Creator
Publisher
Language
Identifier
Keyword
Date created
Related URL
Resource type
Source
  • Angiogenesis (Vol.25)

Rights statement

Relations

Items