Irisin promotes human umbilical vein endothelial cell proliferation through the ERK signaling pathway and partly suppresses high glucose-induced apoptosis

PLoS One. 2014 Oct 22;9(10):e110273. doi: 10.1371/journal.pone.0110273. eCollection 2014.

Abstract

Irisin is a newly discovered myokine that links exercise with metabolic homeostasis. It is involved in modest weight loss and improves glucose intolerance. However, the direct effects and mechanisms of irisin on vascular endothelial cells (ECs) are not fully understood. In the current study, we demonstrated that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) proliferation. It was further demonstrated that this pro-proliferation effect was mediated by irisin-induced activation of extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs. It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression. In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Butadienes / pharmacology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Proliferation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fibronectins / pharmacology*
  • Gene Expression Regulation
  • Glucose / antagonists & inhibitors*
  • Glucose / metabolism
  • Glucose / pharmacology
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Nitriles / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology*
  • Signal Transduction
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • BCL2 protein, human
  • Butadienes
  • FNDC5 protein, human
  • Fibronectins
  • Nitriles
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • U 0126
  • bcl-2-Associated X Protein
  • Extracellular Signal-Regulated MAP Kinases
  • Caspase 3
  • Caspase 9
  • Glucose

Grant support

This work was supported by the Shandong University National Qianren Scholar Fund, and the Taishan Scholar Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.