Angiogenesis is an essential physiological step in wound healing and other regenerative processes. Here, we evaluated the angiogenic properties of an exopolysaccharide (EPS) secreted by MK1 (MK1-EPS), a novel bacterial strain isolated from Neungee mushrooms. MK1-EPS significantly increased human umbilical vein endothelial cell (HUVEC) proliferation, migration, and vascular tube formation. MK1-EPS enhanced the phosphorylation of extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, which are mitogen-activated protein kinases. In addition, the expression of p21 and intercellular adhesion molecule 1 (ICAM1), and phosphorylation of signal transducer and activator of transcription 3 (STAT3), but not of protein kinase B (AKT), were increased. Specific inhibitors of p38 (SB203580), ERK (PD98059), and JNK (SP600125) inhibited MK1-EPS-induced HUVEC proliferation, tube formation, and cell migration, and partially attenuated MKI-EPS-induced expression of p21 and ICAM1, and STAT3 phosphorylation. After surgical implantation into rabbit calvarial bone defects, new blood vessel formation was significantly higher with MK1-EPS composite bone granules than with granules alone, and new bone formation increased significantly. Therefore, MK1-EPS induces angiogenesis and may have potential for use as a bone regeneration agent in bone tissue engineering applications.
Keywords: Angiogenesis; Exopolysaccharide; Human umbilical vein endothelial cell; MK1 bacteria; Signal pathway.