Fetuin-A influences vascular cell growth and production of proinflammatory and angiogenic proteins by human perivascular fat cells
| Autor: | Alfred Königsrainer, Felicia Gerst, Ulrich A. Stock, Christian Klingler, Kilian Rittig, Hans-Eberhard Schaller, Ulrike Schmidt, Birgit Schreiner, Cora Weigert, Dorothea Siegel-Axel, Elko Randrianarisoa, Norbert Stefan, Susanne Ullrich, Hans-Ulrich Häring |
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| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
alpha-2-HS-Glycoprotein Endocrinology Diabetes and Metabolism medicine.medical_treatment Basic fibroblast growth factor Palmitates Receptor tyrosine kinase Proinflammatory cytokine chemistry.chemical_compound Downregulation and upregulation Internal Medicine medicine Humans Angiogenic Proteins Cell Proliferation Glycoproteins Inflammation biology Neovascularization Pathologic Hepatocyte Growth Factor Growth factor Atherosclerosis Coculture Techniques Cell biology Vascular endothelial growth factor Toll-Like Receptor 4 Biochemistry chemistry Adipose Tissue biology.protein Blood Vessels Hepatocyte growth factor Platelet-derived growth factor receptor medicine.drug Signal Transduction |
| Zdroj: | Diabetologia. 57(5) |
| ISSN: | 1432-0428 |
| Popis: | Fetuin-A (alpha2-Heremans-Schmid glycoprotein), a liver-derived circulating glycoprotein, contributes to lipid disorders, diabetes and cardiovascular diseases. In a previous study we found that perivascular fat cells (PVFCs) have a higher angiogenic potential than other fat cell types. The aim was to examine whether fetuin-A influences PVFC and vascular cell growth and the expression and secretion of proinflammatory and angiogenic proteins, and whether TLR4-independent pathways are involved. Mono- and co-cultures of human PVFCs and endothelial cells were treated with fetuin-A and/or palmitate for 6–72 h. Proteins were quantified by ELISA and Luminex, mRNA expression by real-time PCR, and cell growth by BrDU-ELISA. Some PVFCs were preincubated with a nuclear factor κB NFκBp65 inhibitor, or the toll-like receptor 4 (TLR4) inhibitor CLI-095, or phosphoinositide 3-kinase (PI3K)/Akt inhibitors and/or stimulated with insulin. Intracellular forkhead box protein O1 (FoxO1), NFκBp65 and inhibitor of κB kinase β (IKKβ) localisation was visualised by immunostaining. PVFCs expressed and secreted IL-6, IL-8, plasminogen activator inhibitor 1 (PAI-1), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-BB, monocyte chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), placental growth factor (PLGF) and hepatocyte growth factor (HGF). Fetuin-A upregulated IL-6 and IL-8, and this was potentiated by palmitate and blocked by CLI-095. Immunostaining and electrophoretic mobility shift assay (EMSA) showed partial NFκBp65 activation. MCP-1 was upregulated and blocked by CLI-095, but not by palmitate. However, HGF was downregulated, which was slightly potentiated by palmitate. This effect persisted after TLR4 pathway blockade. Stimulation of insulin–PI3K–Akt signalling by insulin resulted in nuclear FoxO1 extrusion and HGF upregulation. Fetuin-A counteracted these insulin effects. Fetuin-A and/or palmitate influence the expression of proinflammatory and angiogenic proteins only partially via TLR4 signalling. HGF downregulation seems to be mediated by interference with the insulin-dependent receptor tyrosine kinase pathway. Fetuin-A may also influence angiogenic and proinflammatory proteins involved in atherosclerosis. |
| Databáze: | OpenAIRE |
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