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dc.contributor.author
Lorenc, Valeria E.  
dc.contributor.author
Subirada Caldarone, Paula Virginia  
dc.contributor.author
Paz, Maria Constanza  
dc.contributor.author
Ferrer, Dario German  
dc.contributor.author
Luna, José Domingo  
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Chiabrando, Gustavo Alberto  
dc.contributor.author
Sanchez, Maria Cecilia  
dc.date.available
2018-05-31T18:12:15Z  
dc.date.issued
2017-01  
dc.identifier.citation
Lorenc, Valeria E.; Subirada Caldarone, Paula Virginia; Paz, Maria Constanza; Ferrer, Dario German; Luna, José Domingo; et al.; IGF-1R Regulates the extracellular level of active MMP-2, pathological neovascularization and functionality in retinas of OIR mouse model; Humana Press; Molecular Neurobiology; 55; 2; 1-2017; 1-13  
dc.identifier.issn
0893-7648  
dc.identifier.uri
http://hdl.handle.net/11336/46843  
dc.description.abstract
In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex. In this study, we used an oxygen-induced retinopathy (OIR) mouse model as well as an in vitro model of hypoxia to study the role of MMP-2 derived from Müller glial cells (MGCs) and its relation with the IGF-1/IGF-1R system. We demonstrated that MMP-2 protein expression increased in P17 OIR mice, which coincided with the active phase of the neovascular process. Also, glutamine synthetase (GS)-positive cells were also positive for MMP-2, whereas IGF-1R was expressed by GFAP-positive cells, indicating that both proteins were expressed in MGCs. In addition, in the OIR model a single intravitreal injection of the IGF-1R blocking antibody (αIR3) administered at P12 effectively prevented pathologic neovascularization, accelerated physiological revascularization, and improved retinal functionality at P17. Finally, in MGC supernatants, the blocking antibody abolished the IGF-1 effect on active MMP-2 under normoxic and hypoxic conditions without affecting the extracellular levels of pro-MMP-2. These results demonstrate, for the first time, that the IGF-1/IGF-1R system regulates active MMP-2 levels in MGCs, thus contributing to MEC remodeling during the retinal neovascular process.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Humana Press  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Muller Glial Cells  
dc.subject
Matrix Metalloprotenases  
dc.subject
Igf 1r  
dc.subject
Hypoxia  
dc.subject.classification
Salud Ocupacional  
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Ciencias de la Salud  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
IGF-1R Regulates the extracellular level of active MMP-2, pathological neovascularization and functionality in retinas of OIR mouse model  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-05-29T20:56:06Z  
dc.identifier.eissn
1559-1182  
dc.journal.volume
55  
dc.journal.number
2  
dc.journal.pagination
1-13  
dc.journal.pais
Estados Unidos  
dc.journal.ciudad
Oregon  
dc.description.fil
Fil: Lorenc, Valeria E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Johns Hopkins University; Estados Unidos  
dc.description.fil
Fil: Subirada Caldarone, Paula Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina  
dc.description.fil
Fil: Paz, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina  
dc.description.fil
Fil: Ferrer, Dario German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina  
dc.description.fil
Fil: Luna, José Domingo. Centro Privado de Ojos Romagosa-fundación Ver; Argentina  
dc.description.fil
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina  
dc.description.fil
Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina  
dc.journal.title
Molecular Neurobiology  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s12035-017-0386-9  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12035-017-0386-9