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

Author:

Kumar V B Sameer12,Viji Raveendran I12,Kiran Manikantan Syamala13,Sudhakaran Perumana R14

Affiliation:

1. Department of Biochemistry, University of Kerala, Thiruvananthapuram 695581, Kerala, India

2. Department of Biological Chemisty, Weizmann Institute of Science, Rehovot 76100, Israel

3. Health Technology Research Center, Hayasi-Cho, Takamastu-Shi, Kagawa 761-0395, Japan

4. School of Biological Sciences, Central University of Kerala, Kasaragod 671123, India

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 E2 (PGE2) increased and that of antiangiogenic PGD2 decreased. The angiogenic effect of PGE2 and PGD2 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 PGE2 and PGD2 in endothelial cells by Ln is mediated through the α6 β4 integrin-p38MAPK (mitogen-activated protein kinase)–NF-κB signaling pathway.

Publisher

SAGE Publications

Subject

General Biochemistry, Genetics and Molecular Biology

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