Differential expression of adenosine receptors in human endothelial cells -: Role of A2B receptors in angiogenic factor regulation
Differential expression of adenosine receptors in human endothelial cells -: Role of A2B receptors in angiogenic factor regulation
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DOI：
10.1161/01.res.0000012203.21416.14
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发表时间：
2002-03-22
影响因子：
20.1
通讯作者：
Biaggioni, I
中科院分区：
文献类型：
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作者：
Feoktistov, I;Goldstein, AE;Biaggioni, I
据报道，腺苷可以刺激或抑制血管生成因子的释放，这取决于所检查的细胞类型。为了验证腺苷受体亚型的差异表达导致内皮细胞异质性的假设，我们研究了微血管（HMEC-1）和脐静脉（HUVEC）人内皮细胞。基于mRNA水平和腺苷酸环化酶的刺激，我们发现HUVECs优先表达A（2A）腺苷受体，HMEC-1优先表达AN受体。两种细胞均不表达A(1)或A(3)受体。非选择性腺苷激动剂5′- n-乙基羧氨基腺苷（NECA）增加了HMEC-1中白细胞介素-8 （IL-8）、碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）的表达，但对huvec没有影响。相比之下，选择性A(2A)，激动剂2-p-（2-羧基乙基）苯乙胺- neca （CGS 21680）对这些血管生成因子的表达没有影响。在HMEC-1中，每种腺苷受体与荧光素酶报告基因共转染表明，a,[，受体激活了IL-8和VEGF启动子，而不是a，， A2A或A3。这些效应被组成活性的alphaG(q)、alphaG（12）和alphaG（13）模仿，但alphaG（13）和alphaG（13）没有。此外，磷脂酶C的刺激表明HMEC-1中A、B受体与G、蛋白偶联。因此，腺苷受体亚型的差异表达导致了人内皮细胞功能的异质性。A(2B)，受体，主要表达于人微血管细胞，通过偶联G调节血管生成因子的表达，也可能通过G调节（12/13）。
Adenosine has been reported to stimulate or inhibit the release of angiogenic factors depending on the cell type examined. To test the hypothesis that differential expression of adenosine receptor subtypes contributes to endothelial cell heterogeneity, we studied microvascular (HMEC-1) and umbilical vein (HUVEC) human endothelial cells. Based on mRNA level and stimulation of adenylate cyclase, we found that HUVECs preferentially express A(2A) adenosine receptors and HMEC-1 preferentially express AN receptors. Neither cells expressed A(1) or A(3) receptors. The nonselective adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased expression of interleukin-8 (IL-8), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in HMEC-1, but had no effect in HUVECs. In contrast, the selective A(2A), agonist 2-p-(2-carboxyethyl)phenylethylamino-NECA (CGS 21680) had no effect on expression of these angiogenic factors. Cotransfection of each type of adenosine receptors with a luciferase reporter in HMEC-1 showed that A,[, receptors, but not A,, A2A, or A3, activated IL-8 and VEGF promoters. These effects were mimicked by constitutively active alphaG(q), alphaG(12), and alphaG(13) but not alphaG(13) or alphaG(13). Furthermore, stimulation of phospholipase C indicated coupling of A,B receptors to G, proteins in HMEC-1. Thus, differential expression of adenosine receptor subtypes contributes to functional heterogeneity of human endothelial cells. A(2B), receptors, predominantly expressed in human microvascular cells, modulate expression of angiogenic factors via coupling to G, and possibly via G(12/13).