Effects and mechanisms of substance P on the proliferation and angiogenic differentiation of bone marrow mesenchymal stem cells: Bioinformatics and in vitro experiments

Abstract

The slight release of substance P (SP) from the end of peripheral nerve fibers causes a neurogenic inflammatory reaction, promotes vascular dilation and increases vascular permeability. However, whether SP can promote the angiogenesis of bone marrow mesenchymal stem cells (BMSCs) under high glucose conditions has not been reported. This study analyzed the targets, biological processes and molecular mechanisms underlying the effects of SP on BMSCs. BMSCs cultured in vitro were divided into a normal control group, high glucose control group, high glucose SP group and high glucose Akt inhibitor group to verify the effects of SP on BMSCs proliferation, migration and angiogenic differentiation. SP was found to act on 28 targets of BMSCs and participate in angiogenesis. Thirty-six core proteins, including AKT1, APP, BRCA1, CREBBP and EGFR, were identified. In a high glucose environment, SP increased the BMSCs proliferation optical density value and cell migration number and reduced the BMSCs apoptosis rate. In addition, SP induced BMSCs to highly express the CD31 protein, maintain the wall structure integrity of the matrix glue mesh and promote increases in the number of matrix glue meshes. These experiments showed that in a high glucose environment, SP acts on 28 targets of BMSCs that encode core proteins, such as AKT1, APP and BRCA1, and improves BMSCs proliferation, migration and angiogenic differentiation through the Akt signaling pathway.