title: NO-dependent proliferation and migration induced by Vitamin D in HUVEC.
abstract: Recently, Vitamin D (Vit. D) has gained importance in cellular functions of a wide range of extraskeletal organs and target tissues, other than bone. In particular, Vit. D has displayed important beneficial effects in the cardiovascular system. Although little is known about the mechanism by which this response is exerted, a Vit. D-induced eNOS-dependent nitric oxide (NO) production in endothelial cells (EC) has been reported. The aim of this study was to evaluate whether Vit. D administration could affect human EC proliferation and/or migration through NO production. For this purpose, HUVEC (human umbilical vein endothelial cells) were used to evaluate Vit. D effects on cell proliferation and migration in a 3D matrix. Experiments were also performed in the presence of the specific VDR ligand ZK159222 and eNOS inhibitor L-NAME. This study demonstrated that Vit. D can promote both HUVEC proliferation and migration in a 3D matrix. These effects were NO dependent, since HUVEC proliferation and migration were abrogated along with Vit. D induced MMP-2 expression by inhibiting eNOS activity by L-NAME. These findings support the role of Vit. D in the angiogenic process, suggesting new applications for Vit. D in tissue repair and wound healing.
authors.affiliation: Innovative Research Laboratory for Wound Healing, Health Sciences Department, University of Eastern Piedmont "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Pittarella
authors.affiliation: Physiology Laboratory, Translational Medicine Department, University of Eastern Piedmont "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Diletta F
authors.initials: DF
authors.lastname: Squarzanti
authors.affiliation: Physiology Laboratory, Translational Medicine Department, University of Eastern Piedmont "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
authors.affiliation: Physical and Rehabilitative Medicine, Health Sciences Department, University of Eastern Piedmont "A. Avogadro", Via Piazza d'Armi 1, 28100 Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Invernizzi
authors.affiliation: Department of Obstetrics and Gynecology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Manfredo Fanti 6, 20122 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Uberti
authors.affiliation: Innovative Research Laboratory for Wound Healing, Health Sciences Department, University of Eastern Piedmont "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy. Electronic address: filippo.reno@med.unipmn.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Renò
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014807:Vitamin D / Q000008:administration & dosage / Q000494:pharmacology*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D014815:Vitamins; D014807:Vitamin D; D009569:Nitric Oxide; D020778:Matrix Metalloproteinase 2
keywords: Cell migration; Endothelial cell; Matrix metalloproteinase-2; Nitric oxide; Vitamin D