Naik Meghna U, Vuppalanchi Deepika, Naik Ulhas P
Department of Biological Sciences, University of Delaware, 329 Wolf Hall, Newark, DE 19716, USA.
Arterioscler Thromb Vasc Biol. 2003 Dec;23(12):2165-71. doi: 10.1161/01.ATV.0000093982.84451.87. Epub 2003 Sep 4.
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.
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.
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.
最近，我们已经表明，阻断连接黏附分子-1/A（JAM-1/A）可抑制碱性成纤维细胞生长因子（bFGF）诱导的血管生成。由于内皮细胞增殖过程是新血管形成的关键起始步骤，我们研究了JAM-1功能敲低对bFGF诱导的人脐静脉内皮细胞（HUVEC）黏附和迁移的影响。
我们将针对JAM-1的小干扰RNA导入HUVECs，用bFGF刺激它们，并研究这些细胞在玻连蛋白和纤连蛋白上的黏附和迁移情况。我们发现，JAM-1的缺失特异性地抑制了bFGF诱导的HUVEC在玻连蛋白上的迁移。这种抑制并非由于连接组织的失败，因为其他连接蛋白的表达和分布仍未受影响。事实上，这种抑制归因于JAM-1缺失的HUVEC无法在玻连蛋白上黏附和铺展。此外，我们发现JAM-1缺失的HUVEC在bFGF处理后未能激活细胞外信号相关激酶（ERK）。
我们的结果表明，JAM-1是bFGF诱导的ERK激活所必需的，而ERK激活会导致内皮细胞在玻连蛋白上迁移。因此，这些数据表明JAM-1是内皮细胞中bFGF和ERK信号通路不可或缺的一部分。
