ZFIN ID: ZDB-PUB-150703-5
RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells
Hoeppner, L.H., Sinha, S., Wang, Y., Bhattacharya, R., Dutta, S., Gong, X., Bedell, V.M., Suresh, S., Chun, C.Z., Ramchandran, R., Ekker, S.C., Mukhopadhyay, D.
Date: 2015
Source: Journal of Cell Science   128(19): 3556-68 (Journal)
Registered Authors: Bedell, Victoria, Chun, Chang Zoon, Ekker, Stephen C., Gong, Xun, Hoeppner, Luke, Mukhopadhyay, Debabrata, Ramchandran, Ramani
Keywords: RhoC, VEGF, Endothelial cell, Migration, Proliferation, Permeability
MeSH Terms:
  • Cell Cycle/genetics
  • Cell Cycle/physiology
  • Cell Movement/genetics
  • Cell Movement/physiology
  • Endothelial Cells/physiology*
  • Humans
  • In Situ Hybridization
  • Signal Transduction*/genetics
  • Signal Transduction*/physiology
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism*
  • rho GTP-Binding Proteins/genetics
  • rho GTP-Binding Proteins/metabolism*
PubMed: 26136364 Full text @ J. Cell Sci.
Vasculogenesis and angiogenesis are controlled by vascular permeability factor/vascular endothelial growth factor A (VEGF). Dysregulation of these physiological processes contributes to the pathologies of heart disease, cancer and stroke. Rho GTPase proteins play an integral role in VEGF-mediated formation and maintenance of blood vessels. The regulatory functions of RhoA and RhoB in vasculogenesis and angiogenesis are well defined, whereas the purpose of RhoC remains poorly understood. Here, we describe how RhoC promotes vascular homeostasis by modulating endothelial cell migration, proliferation, and permeability. RhoC stimulates proliferation of human umbilical vein endothelial cells (HUVEC) by stabilizing nuclear β-catenin, which promotes transcription of cyclin D1 and subsequently drives cell cycle progression. RhoC negatively regulates endothelial cell migration through MAPK and downstream MLC-2 signaling and decreases vascular permeability through downregulation of the phospholipase Cγ (PLCγ)/Ca(2+)/eNOS cascade in HUVEC. Using a VEGF-inducible zebrafish (Danio rerio) model, we observed significantly less vascular permeability in RhoC morpholino (MO)-injected zebrafish than control MO-injected zebrafish. Taken together, our findings suggest RhoC is a key regulator of vascular homeostasis in endothelial cells.