Wound healing is a complex biological process involving vascular remodeling and tissue repair. However, the mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates vascular maturation during wound healing remains unclear. This study aims to investigate the biological mechanism by which GM-CSF promotes vascular maturation and enhances wound repair. Human dermal microvascular endothelial cells (ECs) and human brain vascular pericytes (PCs) were cultured separately or in co-culture and treated with various concentrations of GM-CSF. Cell proliferation and migration were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan and Transwell assays. Tube formation assays were performed to evaluate angiogenic potential. The expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot. Endothelial permeability was analyzed using fluorescein isothiocyanate (FITC)-dextran staining. The expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) was assessed by immunofluorescence. GM-CSF substantially raised EC and PC proliferation and migration in a dose-dependent manner, with more pronounced effects observed in co-culture conditions. GM-CSF grew VEGF and Ang-1 in PCs and enhanced tube formation and barrier integrity in both mono- and co-cultured ECs. Furthermore, GM-CSF-stimulated PC-conditioned medium induced the upregulation of PECAM-1 in ECs. GM-CSF promotes PECAM1 expression, angiogenesis, and vascular maturation in ECs by upregulating VEGF and Ang-1 in PCs. These effects enhance the interaction between endothelial cells and pericytes, thereby contributing to vascular stabilization and improved wound healing. • GM-CSF enhances endothelial and pericyte proliferation and migration. • GM-CSF upregulates VEGF and Ang-1 expression in pericytes. • GM-CSF promotes angiogenesis and stabilizes vascular structure. • GM-CSF facilitates PECAM1 expression in endothelial cells via pericyte signaling.
Ying et al. (Sun,) studied this question.