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

Abstract

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

Methyl 5-Chloro-4,5-didehydrojasmonate (J7) Inhibits Macrophage-Derived Chemokine Production <i>via</i> Down-Regulation of the Signal Transducers and Activators of Transcription 1 Pathway in HaCaT Human Keratinocytes

“…Various studies have reported that several stimuli, including IFN-γ and TNF-α, can also activate the extracellular signal-regulated kinase (ERK), p38 MAPK, and NF-κB pathways. [30][31][32] Under normal conditions, NF-κB combines with inhibitor of kappa B-α (IκB-α) in the cytoplasm. IFN-γ and TNF-α, among other cytokines, can induce the phosphorylation and degradation of IκB-α, leading to the subsequent phosphorylation of NF-κB and its translocation into the nucleus.…”

The role of oncostatin M regulates osteoblastic differentiation of dental pulp stem cells through STAT3 pathway

“…OSM has been known to activate the JAK/ STAT in many kinds of cells (Gomez-Lechon 1999). According to several records, OSM induces JAK1 and JAK2 phosphorylation and activation of STAT2 and STAT3 in vascular smooth muscle cells, and in vascular smooth muscle JAK3 was activated by OSM signaling pathway (Bernard et al 1999;Nagata et al 2003;Demyanets et al 2011). Furthermore, OSM can activate JAK2, JAK3, and stimulate the osteogenic differentiation of human adipose mesenchymal stem cells (hADSCs), increase the expression of osteogenic differentiation markers, such as ALP, RUNX2, osteocalcin and so on (Song et al 2007).…”

STAT3 Protein Regulates Vascular Smooth Muscle Cell Phenotypic Switch by Interaction with Myocardin

“…Correlates with VSMC Synthetic Phenotype-Previous studies have shown that VEGF is a key regulator of physiological and pathological angiogenesis, which inhibits VSMC apoptosis and promotes VSMC proliferation by suppressing the expression of VSMC marker genes (34,35). Our data revealed that although the STAT3 mRNA level in HAVSMCs was not significantly changed after incubating with 50 ng/ml VEGF for different time periods (12,24, and 48 h), the phosphorylated (p)-STAT3 protein expression was significantly elevated to 3-6-fold compared with control levels (Fig.…”