Abstract
Rho GDP-dissociation inhibitor (RhoGDI), a downregulator of Rho family GTPases, prevents nucleotide exchange and membrane association. It is responsible for the activation of Rho GTPases, which regulate a variety of cellular processes, such as migration. Although RhoGDI2 has been identified as a tumor suppressor gene involved in cellular migration and invasion, little is known about its role in vascular endothelial cell (EC) migration. CR6-interacting factor 1 (CRIF1) is a CR6/GADD45-interacting protein with important mitochondrial functions and regulation of cell growth. We examined the expression of RhoGDI2 in CRIF1-deficient human umbilical vein endothelial cells (HUVECs) and its role in cell migration. Expression of RhoGDI2 was found to be considerably higher in CRIF1-deficient HUVECs along with suppression of cell migration. Moreover, the phosphorylation levels of Akt and CREB were decreased in CRIF1-silenced cells. The Akt-CREB signaling pathway was implicated in the changes in endothelial cell migration caused by CRIF1 downregulation. In addition to RhoGDI2, we identified another factor that promotes migration and invasion of ECs. Adrenomedullin2 (ADM2) is an autocrine/paracrine factor that regulates vascular tone and other vascular functions. Endogenous ADM2 levels were elevated in CRIF1-silenced HUVECs with no effect on cell migration. However, siRNA-mediated depletion of RhoGDI2 or exogenous ADM2 administration significantly restored cell migration via the Akt-CREB signaling pathway. In conclusion, RhoGDI2 and ADM2 play important roles in the migration of CRIF1-deficient endothelial cells.
Highlights
We investigated the roles of Rho GDP dissociation inhibitor 2 (RhoGDI2) and ADM2 in the migration of CR6-interacting factor 1 (CRIF1)-deficient human umbilical vein endothelial cells (HUVECs) and the proteins and pathways involved in the process
Cells were seeded in six-well plates, transfected with control or CRIF1 short interfering RNA (siRNA), and incubated for 24 h, after which a scratch was made through the center of each well
The wound area in control siRNA-treated cells was almost covered by migrating cells by 24 h, but an open area remained in the CRIF1 siRNA-treated cells
Summary
Cell motility is essential for the maintenance of normal physiological and pathological processes and proper organization of multi-cellular organisms. Cell migration is fundamental during both embryonic development as well as metastasis of cancer cells. Apart from the development of multi-cellular organisms, cell migration is important for wound healing, tissue homeostasis, and immune responses in physiological conditions, while aberrant cell. Role of CRIF1 deficiency in endothelial cell migration data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
