Department of Biochemistry, University of Kerala, Thiruvananthapuram 695581, Kerala, India.
Exp Biol Med (Maywood). 2011 Jan;236(1):44-51. doi: 10.1258/ebm.2010.010155. Epub 2010 Dec 10.
The molecular mechanism of the angiogenic effect of laminin (Ln) was studied using human umbilical vein endothelial cells (HUVECs) maintained in culture on Ln-1 substratum. High-pressure liquid chromatography analysis showed that in cells maintained on Ln, the levels of proangiogenic prostaglandin E(2) (PGE(2)) increased and that of antiangiogenic PGD(2) decreased. The angiogenic effect of PGE(2) and PGD(2) was confirmed by assessing the expression of CD31 and E-selectin in HUVECs. Immunoblot analysis, reverse transcription-polymerase chain reaction and cyclooxygenase (COX) assay showed increase in the expression and activity of COX-2 in cells maintained on Ln. Use of pharmacological inhibitors suggested that the modulation in the expression of COX-2 and thereby the levels of PGE(2) and PGD(2) in endothelial cells by Ln is mediated through the α(6)β(4) integrin-p38MAPK (mitogen-activated protein kinase)-NF-κB signaling pathway.
采用培养的人脐静脉内皮细胞（HUVEC）在层粘连蛋白（Ln）-1 基质上培养的方法，研究了层粘连蛋白（Ln）促血管生成作用的分子机制。高压液相层析分析表明，在 Ln 维持的细胞中，促血管生成的前列腺素 E2（PGE2）水平增加，而抗血管生成的 PGD2 水平降低。通过评估 HUVEC 中 CD31 和 E-选择素的表达，证实了 PGE2 和 PGD2 的促血管生成作用。免疫印迹分析、逆转录-聚合酶链反应和环氧化酶（COX）测定表明，在 Ln 维持的细胞中 COX-2 的表达和活性增加。药理抑制剂的使用表明，Ln 通过 α6β4 整合素-p38MAPK（丝裂原活化蛋白激酶）-NF-κB 信号通路调节内皮细胞中 COX-2 的表达，从而调节 PGE2 和 PGD2 的水平。
