Published online before print September 4, 2003, doi: 10.1161/01.ATV.0000093982.84451.87
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© 2003 American Heart Association, Inc.
Vascular Biology |
Essential Role of Junctional Adhesion Molecule-1 in Basic Fibroblast Growth Factor–Induced Endothelial Cell Migration
From the Department of Biological Sciences, University of Delaware, Newark, DE.
Correspondence to Ulhas P. Naik, PhD, University of Delaware, Department of Biological Sciences, 329 Wolf Hall, Newark, DE 19716. E-mail unaik{at}udel.edu
Objective— Recently, we have shown that blocking of junctional adhesion molecule-1/A (JAM-1/A) inhibits basic fibroblast growth factor (bFGF)-induced angiogenesis. Because the process of endothelial cell proliferation is a key initial step of neovascularization, we studied the effect of functional knockdown of JAM-1 on human umbilical vein endothelial cell (HUVEC) adhesion and migration induced by bFGF.
Methods and Results— We introduced small interfering RNAs specific to JAM-1 in HUVECs, stimulated them with bFGF, and studied the resultant adhesion and migration of these cells on vitronectin and fibronectin. We show that depletion of JAM-1 inhibits bFGF-induced HUVEC migration specifically on vitronectin. This inhibition is not attributable to the failure of junctional organization, because expression and distribution of other junctional proteins remained unaffected. This inhibition was in fact attributed to an inability of JAM-1–depleted HUVECs to adhere and spread on vitronectin. Furthermore, we find that JAM-1–depleted HUVECs failed to activate extracellular signal–related kinase (ERK) in response to bFGF treatment.
Conclusions— Our results show that JAM-1 is required for the bFGF-induced ERK activation that leads to endothelial cell migration on vitronectin. These data thus implicate JAM-1 as an integral part of both bFGF and ERK signaling pathways in endothelial cells.
Key Words: junctional adhesion molecule-1 • basic fibroblast growth factor • extracellular signal–related kinase • endothelial cell migration • small interfering RNA
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