Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration.
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.
López-Rivera
Esther
E
Fundación Centro Nacional de Investigaciones Cardiovasculares, Ronda de Poniente 5 Tres Cantos, 28760 Madrid, Spain.
Lizarbe
Tania R
TR
Martínez-Moreno
Mónica
M
López-Novoa
José Miguel
JM
Rodríguez-Barbero
Alicia
A
Rodrigo
José
J
Fernández
Ana Patricia
AP
Alvarez-Barrientos
Alberto
A
Lamas
Santiago
S
Zaragoza
Carlos
C
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
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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