title: Hemokinins modulate endothelium function and promote angiogenesis through neurokinin-1 receptor.
abstract: Substance P as a member of tachykinin family plays an important role in angiogenesis. Hemokinins (HKs) have been identified as new members of substance P-like peptides of tachykinin family. However, the effects of HKs on endothelial cells and angiogenesis have not been studied. For the first time, here we demonstrated that r/mHK-1, hHK-1 and hHK(4-11) dose-dependently stimulated the proliferation, migration, adhesion and tube formation of freshly isolated human umbilical vein endothelial cells (HUVECs), and further exhibited in vivo angiogenic effects in chick embryo chorioallantoic membrane model. The angiogenic effects of HKs were inhibited by the selective antagonist of neurokinin-1 rather than neurokinin-2 receptor. Mechanistically, HKs activated ERK1/2 phosphorylation, stimulated nitric oxide production, and upregulated the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in HUVECs. Taken together, our data suggest that HKs emerge as pivotal endogenous regulators of angiogenesis and represent potential targets for the intervention of angiogenesis in different pathological conditions given their specific peripheral distribution.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China. songhj09@lzu.edu.cn
authors.forename: Hongjin
authors.initials: H
authors.lastname: Song
authors.forename: Wen
authors.initials: W
authors.lastname: Yin
authors.forename: Qian
authors.initials: Q
authors.lastname: Zeng
authors.forename: Huazhen
authors.initials: H
authors.lastname: Jia
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.forename: Lingyun
authors.initials: L
authors.lastname: Mu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D015320:Tachykinins / Q000737:chemistry / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; D042461:Vascular Endothelial Growth Factor A; C507968:hemokinin-1; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3