NADPH Oxidase 5 (NOX5) Upregulates MMP-10 Production and Cell Migration in Human Endothelial Cells
Marqués, J. (Universidad de Navarra)
Ainzúa, E. (Universidad de Navarra)
Orbe, J. (Instituto de Salud Carlos III)
Martínez-Azcona, M. (Universidad de Navarra)
Martínez-González, José (Institut de Recerca Sant Pau)
Zalba, G. (Universidad de Navarra)
Universitat Autònoma de Barcelona

Fecha:	2024
Resumen:	NADPH oxidases (NOXs) have been described as critical players in vascular remodeling, a mechanism modulated by matrix metalloproteinases. In this study, we describe for the first time the upregulation of MMP-10 through the activation of NOX5 in endothelial cells. In a chronic NOX5 overexpression model in human endothelial cells, MMP-10 production was measured at different levels: extracellular secretion, gene expression (mRNA and protein levels), and promoter activity. Effects on cell migration were quantified using wound healing assays. NOX5 overexpression increased MMP-10 production, favoring cell migration. In fact, NOX5 and MMP-10 silencing prevented this promigratory effect. We showed that NOX5-mediated MMP-10 upregulation involves the redox-sensitive JNK/AP-1 signaling pathway. All these NOX5-dependent effects were enhanced by angiotensin II (Ang II). Interestingly, MMP-10 protein levels were found to be increased in the hearts of NOX5-expressing mice. In conclusion, we described that NOX5-generated ROS may modulate the MMP-10 expression in endothelial cells, which leads to endothelial cell migration and may play a key role in vascular remodeling.
Ayudas:	Instituto de Salud Carlos III PI22/01450 Agencia Estatal de Investigación PID2021-122509OB-I00
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	AP-1 ; MMP-10 ; NADPH oxidase 5 ; Cell migration ; Endothelial cells ; Oxidative stress
Publicado en:	Antioxidants, Vol. 13 Núm. 10 (october 2024) , p. 1199, ISSN 2076-3921

DOI: 10.3390/antiox13101199
PMID: 39456453

19 p, 4.5 MB

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