Graphene Oxide Accelerate Diabetic Wound Repair by Inhibiting Apoptosis of Ad-MSCs via Linc00324/miR-7977/STK4 Pathway

BackgroundGraphene oxide (GO) has been proven in many studies to promote the proliferation and differentiation of a variety of stem cells, but its effect on the apoptosis of adipose-derived mesenchymal stem cells (Ad-MSCs) is still unclear. Apoptosis is one of the most important factors in the treatment of diabetic wounds by stem cells. Therefore, we explored its therapeutic effect on diabetic wounds by studying the effect of GO on the apoptosis of Ad-MSCs.MethodsqRT-PCR was used to detect the expression of lncRNAs, miRNAs and mRNAs in Ad-MSCs. RNA immunoprecipitation (RIP), RNA pull-down and luciferase assays were used to detect the interaction of the specific lncRNA, miRNA and mRNA. The effects of Linc00324 on Ad-MSCs cells apoptosis were explored by flow cytometer, TUNEL assay and Western blot. Diabetic wound was established to explore the function of Linc00324 on Ad-MSCs repairing ability in vivo.ResultsGO inhibited the apoptosis of Ad-MSCs caused by high glucose, and Linc00324 was one of the factors contributing to its effect. In terms of mechanism, RIP and RNA-Pull-down confirmed Linc00324 could directly interact with miR-7977, and then acted as a miRNA sponge to regulate the expression of miR-7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad-MSCs in wounds and promoted wound healing. ConclusionsOverall, this study highlights that GO maybe a superior auxiliary material for Ad-MSCs to repair diabetic wounds via Linc00324/miR-7977/STK4 pathway.