EPAS1 promotes endothelial cell migration in an IRX3-dependent manner, 2016
Barnett, Petrina K.
2010-2019
Iroquois homeobox gene 3 (Irx3) is a transcription factor belonging to the Iroquois family of homeobox genes that is expressed in the embryonic organs of multiple organisms. Although much is known about Irx3 during embryogenesis, the cross talk of expression and function of Irx3 in peripheral vascular disease (PVD) remains to be investigated. Herein, we demonstrate that Endothelial PAS Domain 1 (EPAS1), which is involved in vasculogenesis and diseases associated with hypoxia, is an upstream regulator of Irx3, and this interaction contributes to the cellular movement of human microvascular endothelial cells (HMVECs). Genetic EPAS1 loss-of-function (LOF) studies in HMVECs resulted in a reduction of Irx3 mRNA, and Irx3-mediated endothelial cell migration in wound healing. In contrast, the effects of EPAS1Gain-of-function (GOF) in HMVECs showed increased Irx3-mediated endothelial cell migration in wound healing. Taken together, these results reveal that Irx3 is an important regulator of cellular movement as a downstream target of EPAS1 signaling in HMVECs, which regulates migration. KEY TERMS: Irx3, EPAS1, Angiogenesis, Cell Migration, HMVEC, Tie2, Biochemistry, Biophysics, and Structural Biology, Biology, Cancer Biology, Cell and Developmental Biology, Diseases, Medicine and Health Sciences, Molecular Biology, Other Cell and Developmental Biology
text
application/pdf
2016-05-16
dissertation
Doctor of Philosophy (PhD)
Clark Atlanta University
Biological Science
Odero-Marah, Valerie Anderson, Leonard M. Hinton, Cimona V.
Georgia--Atlanta
http://hdl.handle.net/20.500.12322/cau.td:2016_barnett_petrina
