title: Irisin Induces Angiogenesis in Human Umbilical Vein Endothelial Cells In Vitro and in Zebrafish Embryos In Vivo via Activation of the ERK Signaling Pathway.
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.
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Song
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Mu
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Jinan Central Hospital Affiliated to Shandong University, Jinan, 250012, P.R. China.
authors.forename: Huanjie
authors.initials: H
authors.lastname: Li
authors.affiliation: Jinan Central Hospital Affiliated to Shandong University, Jinan, 250012, P.R. China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States of America.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States of America.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Urology, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Tang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D015027:Zebrafish
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9