Protective effects of dioscin on vascular remodeling in pulmonary arterial hypertension via adjusting GRB2/ERK/PI3K-AKT signal - 19/12/20
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Graphical abstract |
Highlights |
• | Dioscin ameliorate hypoxia-induced PAH and pulmonary arterial remodeling. |
• | Dioscin inhibit proliferation and migration, induce apoptotic of hypoxic PASMCs. |
• | Dioscin attenuates PAH via regulating GRB2/ERK/PI3K-AKT signal. |
Abstract |
Pulmonary arterial hypertension (PAH) is a progressive and lethal cardiopulmonary. Pulmonary vascular remodeling (PVR) caused by excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) is the chief pathological feature of PAH. Dioscin is a natural product that possesses multiple pharmacological activities, but its effect on PAH remains unclear. In this study, effect of dioscin on vascular remodeling in PAH was assessed in hypoxia-induced PASMCs, hypoxia-induced and monocrotaline (MCT)-induced rats. Western blot, Real-time PCR and siRNA transfection tests were applied to evaluate the possible mechanisms of dioscin. In vitro experiments, results showed dioscin markedly inhibited the proliferation and migration, and promoted apoptosis of hypoxic PASMCs. In vivo, dioscin significantly decreased the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI), and improved pulmonary vascular stenosis in rats induced by hypoxia or MCT. Molecular mechanism studies showed that dioscin significantly reduced the expression of growth factor receptor-bound protein 2 (GRB2). Subsequently, dioscin reduced the expressions of Ras, Cyclin D1, CDK4, c-Fos, PCNA and p-ERK to inhibit proliferation and migration of PASMCs, inhibited p-PI3K and p-AKT levels and increased Bax/Bcl2 ratio to promote cell apoptosis. GRB2 siRNA transfection in PASMCs further confirmed that the inhibitory action of dioscin in PAH was evoked by adjusting GRB2/ERK/PI3K-AKT signal. Taken together, our study indicated that dioscin attenuates PAH through adjusting GRB2/ERK/PI3K-AKT signal to inhibit PASMCs proliferation and migration, and promote apoptosis, and dioscin may be developed as a therapeutic strategy for treating PAH in the future.
El texto completo de este artículo está disponible en PDF.Abbreviation : 5-HT, AKT, CDK4, CMC-Na, DAPI, DMEM, DMSO, ERK, ET-1, FBS, HSYA, Hyp, GRB2, MAPKs, MCT, PAH, PAs, PASMCs, PCNA, PDGF, PI3K, PMSF, PVR, RVHI, RVSP, siRNA
Keywords : Vascular remodeling, Pulmonary arterial smooth muscle cells, Dioscin, Molecular mechanism, GRB2/ERK/PI3K-AKT signal
Esquema
Vol 133
Artículo 111056- janvier 2021 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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