Exenatide can inhibit calcification of human VSMCs through the NF-kappaB/RANKL signaling pathway.
Cardiovasc Diabetol
; 13: 153, 2014 Nov 19.
Article
en En
| MEDLINE
| ID: mdl-25407893
ABSTRACT
BACKGROUND:
Arterial calcification is an important pathological change of diabetic vascular complication. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important cytopathologic role in arterial calcification. The glucagon-like peptide-1 receptor agonists (GLP-1RA), a novel type of antidiabetic drugs, exert cardioprotective effects through the GLP-1 receptor (GLP-1R). However, the question of whether or not GLP-1RA regulates osteoblastic differentiation and calcification of VSMCs has not been answered, and the associated molecular mechanisms have not been examined.METHODS:
Calcifying VSMCs (CVSMCs) were isolated from cultured human arterial smooth muscle cells through limiting dilution and cloning. The extent of matrix mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot. Gene expression of receptor activator of nuclear factor-κB ligand (RANKL) was silenced by small interference RNA (siRNA).RESULTS:
Exenatide, an agonist of GLP-1 receptor, attenuated ß-glycerol phosphate (ß-GP) induced osteoblastic differentiation and calcification of human CVSMCs in a dose- and time-dependent manner. RANKL siRNA also inhibited osteoblastic differentiation and calcification. Exenatide decreased the expression of RANKL in a dose-dependent manner. 1,25 vitD3 (an activator of RANKL) upregulated, whereas BAY11-7082 (an inhibitor of NF-κB) downregulated RANKL, alkaline phosphatase (ALP), osteocalcin (OC), and core binding factor α1 (Runx2) protein levels and reduced mineralization in human CVSMCs. Exenatide decreased p-NF-κB and increased p-AMPKα levels in human CVSMCs 48 h after treatment. Significant decrease in p-NF-κB (p-Ser(276), p-Ser(536)) level was observed in cells treated with exenatide or exenatide + BAY11-7082.CONCLUSION:
GLP-1RA exenatide can inhibit human VSMCs calcification through NF-κB/RANKL signaling.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
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Ponzoñas
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Calcificación Fisiológica
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Transducción de Señal
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FN-kappa B
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Ligando RANK
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Calcificación Vascular
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Músculo Liso Vascular
Límite:
Humans
Idioma:
En
Revista:
Cardiovasc Diabetol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
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ENDOCRINOLOGIA
Año:
2014
Tipo del documento:
Article