Oncostatin M-enhanced vascular endothelial growth factor expression in human vascular smooth muscle cells involves PI3K-, p38 MAPK-, Erk1/2- and STAT1/STAT3-dependent pathways and is attenuated by interferon-γ

摘要: The pleiotropic cytokine oncostatin M (OSM), a member of the glycoprotein (gp)130 ligand family, plays key role in inflammation and cardiovascular disease. As precedes accompanies pathological angiogenesis, we investigated effect OSM other gp130 ligands on vascular endothelial growth factor (VEGF) production human smooth muscle cells (SMC). Human coronary artery SMC (HCASMC) aortic (HASMC) were treated with different ligands. VEGF protein was determined by ELISA. Specific mRNA detected RT-PCR. Western blotting performed for signal transducers activators transcription1 (STAT1), STAT3, Akt p38 mitogen-activated kinase (p38 MAPK). expression analyzed carotid endaterectomy specimens from 15 patients. increased both HCASMC HASMC derived donors. upregulated receptor-specific these cells. STAT3 inhibitor WP1066, MAPK inhibitors SB-202190 BIRB 0796, extracellular signal-regulated kinase1/2 (Erk1/2) U0126, phosphatidylinositol 3-kinase (PI3K) LY-294002 PI-103 reduced OSM-induced synthesis. We found atherosclerotic lesions where correlated expression. Interferon-γ (IFN-γ), but not IL-4 or IL-10, SMC. Our findings that OSM, which is present correlates expression, stimulates indicate could contribute to plaque angiogenesis destabilization. IFN-γ