Abstract
As a link between exercise and metabolism, irisin is assumed to be involved in increased total body energy expenditure, reduced body weight, and increased insulin sensitivity. Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive. In the current study, it was found that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) angiogenesis via increasing migration and tube formation, and attenuated chemically-induced intersegmental vessel (ISV) angiogenic impairment in transgenic TG (fli1: GFP) zebrafish. It was further demonstrated that expression of matrix metalloproteinase (MMP) 2 and 9 were also up-regulated in endothelial cells. We also found that irisin activated extracellular signal–related kinase (ERK) signaling pathways. Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC. Also, U0126 inhibited the elevated expression of MMP-2 and MMP-9 when they were treated with irisin. In summary, these findings provided direct evidence that irisin may play a pivotal role in maintaining endothelium homeostasis by promoting endothelial cell angiogenesis via the ERK signaling pathway.
Highlights
Angiogenesis, the sprouting of pre-existing vasculature to form new vessels, requires many coordinated endothelial cell activities, such as proliferation, migration, and alignment to form vessel-like tube structures [1,2,3]
(Fig 1D and 1E), and the difference was statistically significant (P < 0.01).These results indicated that irisin has the ability to enhance endothelial cell migration
To determine which matrix metalloproteinase (MMP) can be influenced by irisin in Human Umbilical Vein Endothelial Cell (HUVEC), we examined mRNA expression of MMPs and other genes which may play a critical role in the progress of cells migration
Summary
Angiogenesis, the sprouting of pre-existing vasculature to form new vessels, requires many coordinated endothelial cell activities, such as proliferation, migration, and alignment to form vessel-like tube structures [1,2,3]. We demonstrated the effect of irisin in promoting HUVEC proliferation via the ERK signaling pathway and that it partially protects the cell from high glucose-induced apoptosis [15]. These finding suggest that there is a link between irisn and the vascular endothelium. No previous studies have evaluated whether irisin directly regulates other functions of human ECs such as migration and angiogenesis
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