ZFIN ID: ZDB-PUB-150805-1
Irisin Induces Angiogenesis in Human Umbilical Vein Endothelial Cells In Vitro and in Zebrafish Embryos In Vivo via Activation of the ERK Signaling Pathway
Wu, F., Song, H., Zhang, Y., Zhang, Y., Mu, Q., Jiang, M., Wang, F., Zhang, W., Li, L., Li, H., Wang, Y., Zhang, M., Li, S., Yang, L., Meng, Y., Tang, D.
Date: 2015
Source: PLoS One   10: e0134662 (Journal)
Registered Authors: Wang, Fang
Keywords: Angiogenesis, Zebrafish, ERK signaling cascade, Endothelial cells, Cell migration, Embryos, MPK signaling cascades, Extracellular matrix
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Movement/drug effects*
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Fibronectins/pharmacology*
  • Human Umbilical Vein Endothelial Cells/drug effects*
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • MAP Kinase Signaling System/drug effects*
  • Matrix Metalloproteinase 2/metabolism
  • Matrix Metalloproteinase 9/metabolism
  • Neovascularization, Physiologic/drug effects*
  • Up-Regulation/drug effects
  • Zebrafish
PubMed: 26241478 Full text @ PLoS One
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.