Abstract
The proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. In the present study, the effect of paeoniflorin (PAE) on the platelet derived growth factor‑BB (PDGF‑BB)‑induced proliferation of primary cultured rat VSMCs and its molecular mechanism was investigated. The toxicity was determined by the try pan blue exclusion test. Cell proliferation was determined using a CCK‑8 assay, DNA synthesis was assessed by measuring the incorporation of BrdU. Cell cycle progression was determined using PI staining and fluorescence‑activated cell sorting. The level of intracellular reactive oxygen species (ROS) generation was assessed using dichlorodihydro fluorescein diacetate. mRNA expression was determined by reverse transcription quantitative polymerase chain reaction. Changes of p38, JNK, ERK1/2 signaling pathways were determined by western blot analysis. Cell migration was detected by scratch assay. PAE was demonstrated to significantly inhibit VSMC proliferation induced by PDGF‑BB in a dose‑and time‑dependent manner without cell cytotoxicity. Thus, PAE blocked progression through the G0/G1 to Sphase of the cell cycle. Furthermore, inhibition of the cell cycle was associated with the inhibition of them RNA expression of cyclin D1, cyclin E, cyclin dependent kinase (CDK) 4 and CDK2 as well as with increased cyclin dependent kinase inhibitor 1A mRNA expression in PDGF‑BB‑stimulated VSMCs. Further studies showed that the beneficial effect of PAE on blocking VSMCs proliferation was related to the suppression of the ROS‑mediated extra cellular signal‑regulated kinase (ERK)1/2 and p38 signaling pathways, although PAE had no significant effect on the c‑Jun N‑terminal kinase signalling pathway. These results demonstrated that PAE suppressed PDGF‑BB‑induced VSMC proliferation through the ROS‑mediated ERK1/2 and p38 signaling pathways, suggesting that it may be a feasible therapy for vascular remodelling diseases.