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Título: | Inhibition of protein tyrosine phosphatase 1B improves IGF-I receptor signaling and protects against inflammation-induced gliosis in the retina |
Autor: | Arroba, Ana I. CSIC ORCID; Valverde, Ángela M. CSIC ORCID | Fecha de publicación: | 2016 | Citación: | CIBERDEM Annual Meeting (2016) | Resumen: | [Purpose]: Insulin like growth factor-I receptor (IGF-IR)-mediated signaling plays an important role in retinal growth and survival and its failure may contribute to aggravate diabetic retinopathy (DR). Protein tyrosine phosphatase 1B (PTP1B) has emerged as a negative modulator of IGF-IR-mediated signaling but its role in the context of the proinflammatory milieu during DR remains unknown. We investigated the involvement of PTP1B in the cross-talk between stress pathways activated by proinflammatory cytokines and IGF-IR-mediated signaling in the retina. [Methods]: We treated 661W photoreceptors and retinal explants with a mixture of cytokines containing tumor necrosis factor α (TNFα), interleukin 6 (IL6) and interleukin 1β (IL1β), and the IGF-IR signaling cascade was evaluated in the absence or presence of PTP1B. [Results]: 661W retinal cells and retinal explants were sensitive to IGF-I in inducing IGF-IR and Akt phosphorylation. Stimulation with cytokines triggered an early activation of stress kinases (JNK and p38 MAPK), resulting in insulin receptor substrate 1 (IRS1) phosphorylation at serine 307 that precedes its degradation. Pre-treatment of 661W cells or retinal explants with cytokines for 24 hours induced IRS1 degradation and decreased IGF-I-mediated IGF-IR and Akt phosphorylation. PTP1B siRNA or PTP1B deficiency ameliorated the negative effects of cytokines on IGF-IR signaling. Treatment with cytokines increased GFAP expression in retinal explants and this response was ameliorated by a PTP1B inhibitor. GFAP was also reduced by the PTP1B inhibitor in retinas from db/db mice. [Conclusions]: Targeting PTP1B might be useful for modulating the beneficial effects of IGF-I in retinal cells during DR. | Descripción: | Resumen del póster presentado presentado al CIBERDEM Annual Meeting, celebrado en Cerdanyola del Vallès, Barcelona (España) del 11 al 13 de mayo de 2016. | URI: | http://hdl.handle.net/10261/160698 |
Aparece en las colecciones: | (IIBM) Comunicaciones congresos |
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