Yeast-derived particulate beta-glucan induced angiogenesis via regulating PI3K/Src and ERK1/2 signaling pathway.

ABSTRACT

The importance of ß-glucan from S. cerevisiae in angiogenesis has not been well studied. We investigated whether ß-glucan induces angiogenesis through PI3K/Src and ERK1/2 signaling pathway in HUVECs. We identified that ß-glucan induced phosphorylation of PI3K, Src, Akt, eNOS, and ERK1/2. Subsequently, we found that this phosphorylation increased the viability of HUVECs. We also observed that stimulation of ß-glucan promoted the activity of MEF2 and MEF2-dependent pro-angiogenic genes, including EGR2, EGR3, KLF2, and KLF4. Additionally, the role of ß-glucan in angiogenesis was confirmed using in vitro and ex vivo experiments including cell migration, capillary-like tube formation and mouse aorta ring assays. To determine the effect of ß-glucan on the PI3K/Akt/eNOS and ERK1/2 signaling pathway, PI3K inhibitor wortmannin and ERK1/2 inhibitor SCH772984 were used. Through the Matrigel plug assay, we confirmed that ß-glucan significantly increased angiogenesis in vivo. Taken together, our study demonstrates that ß-glucan promotes angiogenesis via through PI3K and ERK1/2 signaling pathway.