title: Angiogenic effect of laminin involves modulation of cyclooxygenase-2 and prostaglandin levels.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Kerala, Thiruvananthapuram 695581, Kerala, India.
authors.forename: V B Sameer
authors.initials: VB
authors.lastname: Kumar
authors.forename: Raveendran I
authors.initials: RI
authors.lastname: Viji
authors.forename: Manikantan Syamala
authors.initials: MS
authors.lastname: Kiran
authors.forename: Perumana R
authors.initials: PR
authors.lastname: Sudhakaran
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000502:physiology*; D015232:Dinoprostone / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007797:Laminin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000187:drug effects / Q000502:physiology
chemical_list: D007797:Laminin; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D015230:Prostaglandin D2