Angiogenic effect of laminin involves modulation of cyclooxygenase-2 and prostaglandin levels.

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)ß(4) integrin-p38MAPK (mitogen-activated protein kinase)-NF-κB signaling pathway.