Salidroside blocks the proliferation of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB

Abstract

The proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the development of pulmonary vascular remodeling, ultimately leading to pulmonary hypertension. In this study, the effects and molecular mechanisms of salidroside on the platelet‑derived growth factor (PDGF)‑BB‑induced proliferation of primary cultured rat PASMCs were investigated. The presented data demonstrated that salidroside significantly inhibited the proliferation and DNA synthesis of PASMCs induced by PDGF‑BB in a dose‑ and time‑dependent manner, without cell cytotoxicity. In accordance with these findings, salidroside blocked progression through G0/G1 to S phase of the cell cycle. The salidroside‑induced inhibition of the cell cycle was associated with the inhibition of cyclin D1, cyclin E, cyclin‑dependent kinase 2 (CDK2) and CDK4 mRNA expression, as well as an increase in the mRNA expression of p27 in PDGF‑BB‑stimulated PASMCs. Further experiments showed that the beneficial effect of salidroside on blocking the proliferation of PASMCs was associated with the suppression of the AKT/glycogen synthase kinase 3 β (GSK3β) signaling pathway, but did not involve the extracellular signal‑regulated kinase 1/2, p38 and c‑Jun‑N‑terminal kinase signaling pathways. These results indicate that salidroside suppresses PDGF‑BB‑induced PASMC proliferation through the AKT/GSK3β signaling pathway and suggests that it may be a feasible therapy for pulmonary vascular remodeling diseases.

Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells

“…In cell study of present study, we administrated 100 μM salidroside to cultured cerebral VSMCs for 48 h under hyperglycemia in vitro. The concentration of salidroside (100 μM) in our study is same to the previous report that 100 μM salidroside blocks the proliferation of pulmonary artery smooth muscle cells (PASMCs) induced by platelet-derived growth factor-BB in vitro [42]. In addition, the concentration of salidroside (100 μM) in our study is also similar to the previous report that 800 μM salidroside modulated cell apoptosis in mouse cultured pulmonary arterial smooth muscle cells (PASMCs) after chronic hypoxia exposure in vitro [10].…”

Salidroside attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2a receptor related mitochondria-dependent apoptosis pathway

“…Recent studies indicate that salidroside can rescue mitochondria dysfunction induced by stimuli in human umbilical vein endothelial cells (HUVECs) [23] and block platelet-derived growth factor-BB induced proliferation of PASMCs [24], suggesting that salidroside may, via rebalancing cell proliferation and mitochondria-dependent apoptosis of pulmonary artery cells, exert protective effects against PAH. However, specific function of salidroside in PAH has not been investigated systematically and the underlying mechanisms are not explored.…”

“…Several experimental and clinical studies of salidroside have provide evidences for its multiple pharmacological activities including anti-inflammation [19], anti-oxidation [20], anti-stress, anti-cancer, and enhancing immune effects [18,21,22]. Recent studies indicate that salidroside can rescue mitochondria dysfunction induced by stimuli in human umbilical vein endothelial cells (HUVECs) [23], and also salidroside can block platelet-derived growth factor-BB induced proliferation of PASMCs [24], suggesting that salidroside may exert protective effects against PAH via rebalancing cell proliferation and apoptosis of pulmonary artery cells. However, the function of salidroside in PAH has not been investigated systematically and the underlying mechanisms are not clear.…”

Effects of hesperetin on platelet-derived growth factor-BB-induced pulmonary artery smooth muscle cell proliferation

“…PASMCs was determined using the trypan blue exclusion method (Sinopharm Chemical Reagent Co.). After 12-, 24-and 48-h incubations with hesperetin (12.5-100 µM), the PASMCs were removed from the culture and the cells that excluded 0.4% trypan blue were counted in an automated cell counter (Invitrogen; Thermo Fisher Scientific, Inc.) (21).…”

“…After 4-5 days, the cells were passaged and grown in DMEM/F12 supplemented with 10% FBS. The purity of the PASMC cultures was assessed by immunocytochemical localization of α-smooth muscle actin according to a previously described procedure (21). The cells from passages 4 and 10 were used in the present study.…”