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Receptor tyrosine kinase Tie-1 overexpression in endothelial cells upregulates adhesion molecules
Authors:Chan Barden  Yuan Hai-Tao  Ananth Karumanchi S  Sukhatme Vikas P
Affiliation:a Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RW 563, Boston, MA 02215, USA
b Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RW 563, Boston, MA 02215, USA
Abstract:Tie-1 is an endothelial specific cell surface protein whose biology remains poorly understood. Using an overexpression system in vitro, we examined whether Tie-1 activity in endothelial cells in vitro would elicit a proinflammatory response. We found that when overexpressed in endothelial cells in vitro, Tie-1 is tyrosine-phosphorylated. We also showed that Tie-1 upregulates VCAM-1, E-selectin, and ICAM-1, partly through a p38-dependent mechanism. Interestingly, upregulation of VCAM-1 and E-selectin by Tie-1 is significantly higher in human aortic endothelial cells than in human umbilical vein endothelial cells. Additionally, attachment of cells of monocytic lineage to endothelial cells is also enhanced by Tie-1 expression. Collectively, our data show that Tie-1 has a proinflammatory property and may play a role in the endothelial inflammatory diseases such as atherosclerosis.
Keywords:Atherosclerosis   Adhesion molecules   Tie-1
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