Electrical stimulation facilitates the angiogenesis of human umbilical vein endothelial cells through MAPK/ERK signaling pathway by stimulating FGF2 secretion

Abstract

Electrical stimulation (ES) is able to enhance angiogenesis by stimulating fibroblasts. Fibroblast growth factor 2 (FGF2) is an independent angiogenesis inducer. The present study aimed to evaluate the role of ES-induced FGF2 secretion in affecting angiogenesis during wound healing via the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Fibroblasts and human umbilical vein endothelial cells (HUVECs) were exposed to ES, and the HUVECs were cocultured with ES-treated fibroblast culture solution. ES exposure showed no toxic effects on fibroblasts or HUVECs. ES led to enhanced growth of fibroblasts and HUVECs as well as FGF2 secretion, which is induced through the NOS pathway. ES-induced FGF2 secretion was shown to increase vascular endothelial growth factor (VEGF) protein and enhance migration, invasion, and angiogenesis of HUVECs. Also, ES-induced FGF2 secretion activated the MAPK/ERK signaling pathway. However, inhibition of the MAPK/ERK signaling pathway reversed the positive effects of ES-induced FGF2 secretion. In vitro experiments showed positive effects of ES on wound healing. Taken together, the findings suggested that ES promoted FGF2 secretion and then activated the MAPK/ERK signaling pathway by facilitating angiogenesis and promoting wound healing.

Electrical Stimulation to Enhance Wound Healing

“…In summary, the growth factors noted to be enhanced upon ES across the reviewed studies are FGF-1, FGF-2, and VEGF. These collectively aid in the proliferation of endothelial cells, fibroblasts, and expedites new vessel formation [ 51 ]. Table 4 summarizes key findings of in vivo and in vitro studies that investigate the effect of ES on this phase of healing [ 43 , 44 , 45 , 46 , 47 , 48 , 49 ].…”

Analysis of the Differential Gene and Protein Expression Profiles of Corneal Epithelial Cells Stimulated with Alternating Current Electric Fields

“…Further, DC-induced activation of the PI3K/AKT pathway was also reported in different cell types, including neural progenitor cells [ 47 ], Schwann cells [ 48 ], and human umbilical vein endothelial cells (HUVEC) [ 49 ], as well as in ocular cells, including the corneal epithelium [ 6 , 50 ]. Activation of the MAPK signaling pathway is also reported through the application of EFs in neuronal cells [ 51 , 52 ], fibroblasts, HUVEC [ 53 ], and corneal epithelial cells [ 6 ]. Likewise, we also observed activation of PI3K/AKT and MAPK signaling pathways, along with other interconnected pathways, including T cell receptor signaling, Toll-like receptor signaling, TNF signaling, IL-17 signaling, FoxO signaling, and focal adhesion pathways, upon stimulation of corneal epithelial cells with oscillating EFs.…”

Exosomal CLIC1 released by CLL promotes HUVECs angiogenesis by regulating ITGβ1‐MAPK/ERK axis

“…MAPK/ERK signaling pathway is critical component in various processes including differentiation, proliferation, migration, and angiogenesis in a variety of human diseases development 31,32 . Clinical heterogeneity study on CLL showed that aberrant activation of MAPK‐ERK signaling promoted CLL cells proliferation and survival, and was closely related the dysregulation of homeostatic mechanisms in CLL cells 33 .…”