Resveratrol-laden mesoporous silica nanoparticles regulate the autophagy and apoptosis via ROS-mediated p38-MAPK/HIF-1a /p53 signaling in hypertrophic scar fibroblasts

BackgroundDuring the regression of hypertrophic scars, autophagy and apoptosis are the main ways of cell death. Recent investigations demonstrated effective inhibition of resveratrol on hypertrophic scar fibroblasts (HSFs). But its therapeutic value is limited by chemical instability and hydrophobicity, as well as the mechanism of its role in regulation of autophagy and apoptosis remains unknown.Aim of the studyWe prepared a mesoporous silica nanoparticle laden with resveratrol (MSNs@Res) which can effectively improve the solubility and stability of resveratrol. The purpose of this study was to investigate whether MSNs@Res regulates autophagy and apoptosis of HSFs via inhibition of ROS/p38/HIF-1α/p53 signaling axis, as to reveal its pharmacological action and target.Materials and methodsNetwork pharmacology, molecular docking, and in vitro assays were carried out in this study. An in vitro model of fibroblasts cultivated in hypoxic and ischemic situations was established to simulate the scar in the proliferative phase.ResultsMSNs@Res surpresses HSFs by reducing protective autophagy and inducing apoptosis, autosis may be another cell death involed in this process. According to the network pharmacological analysis and molecular docking, the mechanism by which MSNs@Res alleviates hypertrophic scar may be closely related to the MAPK signaling pathway. MSNs@Res significantly downregulate the expression of HIF-1α and p53 through the inhibition of ROS induced p38-MAPK phosphorylation with corresponding changes in the expression of autophagy and apoptosis related protein.ConclusionMSNs@Res is a novel drug delivery system with excellent chemical stability and drug release performance. It can inhibit protective autophagy of fibroblasts in hypoxic environment, and induce the apoptosis and autosis via the ROS -mediated p38-MAPK/HIF-1α/p53 signaling axis.