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Título:	Uridine 5'-triphosphate promotes in vitro Schwannoma cell migration through matrix metalloproteinase-2 activation
Autor/a:	Lamarca Dams, Aloa; Gella Concustell, Alejandro; Martiáñez Canales, Tània; Segura Castell, Mónica; Figueiro-Silva, Joana; Grijota Martínez, Maria del Carmen; Trullás, Ramón; Casals i Farré, Núria
Notas:	In response to peripheral nerve injury, Schwann cells adopt a migratory phenotype and modify the extracellular matrix to make it permissive for cell migration and axonal re-growth. Uridine 5′-triphosphate (UTP) and other nucleotides are released during nerve injury and activate purinergic receptors expressed on the Schwann cell surface, but little is known about the involvement of purine signalling in wound healing. We studied the effect of UTP on Schwannoma cell migration and wound closure and the intracellular signaling pathways involved. We found that UTP treatment induced Schwannoma cell migration through activation of P2Y2 receptors and through the increase of extracellular matrix metalloproteinase-2 (MMP-2) activation and expression. Knockdown P2Y2 receptor or MMP-2 expression greatly reduced wound closure and MMP-2 activation induced by UTP. MMP-2 activation evoked by injury or UTP was also mediated by phosphorylation of all 3 major mitogen-activated protein kinases (MAPKs): JNK, ERK1/2, and p38. Inhibition of these MAPK pathways decreased both MMP-2 activation and cell migration. Interestingly, MAPK phosphorylation evoked by UTP exhibited a biphasic pattern, with an early transient phosphorylation 5 min after treatment, and a late and sustained phosphorylation that appeared at 6 h and lasted up to 24 h. Inhibition of MMP-2 activity selectively blocked the late, but not the transient, phase of MAPK activation. These results suggest that MMP-2 activation and late MAPK phosphorylation are part of a positive feedback mechanism to maintain the migratory phenotype for wound healing. In conclusion, our findings show that treatment with UTP stimulates in vitro Schwannoma cell migration and wound repair through a MMP-2-dependent mechanism via P2Y2 receptors and MAPK pathway activation.
Materia(s):	-Cèl·lules -- Migració -Cicatrització -Fluorescència -Expressió gènica -Nucleòtids -- Anàlisi -Fosforilació -Células -Cicatrización -Fluorescencia -Expresión génica -Nucleótidos -Fosforilación oxidativa -Schwann Cells -- Pathology -Cell migration -Wound healing -MAPKs (Enzymes) -Fluorescence microscopy -Gene expression -Nucleotide -Phosphorylation -61
Derechos:	© 2014 Lamarca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Tipo de documento:	Artículo Artículo - Versión aceptada
Editor:	Public Library of Science
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