title: Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration.
abstract: To explore the mechanisms by which NO elicits endothelial cell (EC) migration we used murine and bovine aortic ECs in an in vitro wound-healing model. We found that exogenous or endogenous NO stimulated EC migration. Moreover, migration was significantly delayed in ECs derived from endothelial NO synthase-deficient mice compared with WT murine aortic EC. To assess the contribution of matrix metalloproteinase (MMP)-13 to NO-mediated EC migration, we used RNA interference to silence MMP-13 expression in ECs. Migration was delayed in cells in which MMP-13 was silenced. In untreated cells MMP-13 was localized to caveolae, forming a complex with caveolin-1. Stimulation with NO disrupted this complex and significantly increased extracellular MMP-13 abundance, leading to collagen breakdown. Our findings show that MMP-13 is an important effector of NO-activated endothelial migration.
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares, Ronda de Poniente 5 Tres Cantos, 28760 Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: López-Rivera
authors.forename: Tania R
authors.initials: TR
authors.lastname: Lizarbe
authors.forename: Mónica
authors.initials: M
authors.lastname: Martínez-Moreno
authors.forename: José Miguel
authors.initials: JM
authors.lastname: López-Novoa
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Barbero
authors.forename: José
authors.initials: J
authors.lastname: Rodrigo
authors.forename: Ana Patricia
authors.initials: AP
authors.lastname: Fernández
authors.forename: Alberto
authors.initials: A
authors.lastname: Alvarez-Barrientos
authors.forename: Santiago
authors.initials: S
authors.lastname: Lamas
authors.forename: Carlos
authors.initials: C
authors.lastname: Zaragoza
mesh_terms: D000818:Animals; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins / Q000502:physiology; D002465:Cell Movement; D017364:Collagenases / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology*; D053509:Matrix Metalloproteinase 13; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014945:Wound Healing
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse
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