Irisin Promotes Human Umbilical Vein Endothelial Cell Proliferation through the ERK Signaling Pathway and Partly Suppresses High Glucose-Induced Apoptosis

• DOI: 10.1371/journal.pone.0110273
• Publication Date: 2014-10-22T17:54:17Z
• Authors: Haibo Song; Fei Wu; Yuan Zhang; Yuzhu Zhang; Fang Wang; Miao Jiang; Zhongde Wang; Mingxiang Zhang; Shiwu Li; Lijun Yang; Xing Li Wang; Taixing Cui; Dongqi Tang
• Keywords: 0301 basic medicine; Caspase 3; Science; Q; R; Apoptosis; Caspase 9; Recombinant Proteins; Fibronectins; 03 medical and health sciences; Glucose; Gene Expression Regulation; Proto-Oncogene Proteins c-bcl-2; Nitriles; Butadienes; Human Umbilical Vein Endothelial Cells; Medicine; Humans; Extracellular Signal-Regulated MAP Kinases; Protein Kinase Inhibitors; Research Article; Cell Proliferation; Signal Transduction; bcl-2-Associated X Protein

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.