CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Insulin-Like Growth Factor 1 (IGF-1) Modulate Migratory Capacity of Glial Muller Cells Through the Activation of Metalloproteinase-2 (MMP-2).
Autor/es:
LORENC VE; ORTIZ S; CHIABRANDO GA; SANCHEZ MC
Lugar:
Fort Lauderdale
Reunión:
Otro; ARVO´s 2010Annual Meeting (The Association for Research in Vision and Ophthalmology; 2010
Resumen:
Purpose: IGF-1 has an active participation during the normal retinal vascular development of the retina as well as in the pathogenesis of retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR). Glial Müller cells (MC) are known to be involved in these diseases by producing Vascular Endothelial Growth Factor (VEGF) and secreting MMPs that participate in the extracellular proteolysis during neovascularization. However, at present, is not well elucidated the function of IGF-1 during this process. In this work we evaluate the effect of IGF-1 on the regulation of MMPs and on the migratory capacity of an immortalized human Müller cells line, MIO-M1. Methods: The human MIO-M1 was cultured in the absence or presence of 10 nM IGF-1 for different time periods (4, 6 and 8 h). The effect of IGF-1 on MMPs activity was evaluated in MC supernatants by zymography. The expression level of MT1-MMP and MMP-2 was analyzed by Western blot (WB) analysis. Cell migration was evaluated on collagen or laminin-coated surface using time-lapse video microscopy. The IGF-1 induced signalling pathways were evaluated by WB. Results: By zymography we observed that IGF-1 increased pro-MMP-2 activity whereas MMP-2 activity was decreased trough time of stimulus. By WB we observed that, under  IGF-1 stimulus, MMP-2 increased in the lysates and decreased in the supernatants in concordance with obtained by zimography. IGF-1 also produced an activation of the MAPK-ERK1/2 y PI3K/Akt pathway indicating that these transduction events may be mediated by IGF-1 receptors. MT1-MMP protein, which was associated with the MMP-2 activity was decreased in the stimulated cells. This MMPs regulation was also accompanied by an increase of cell motility on coated surfaces. Conclusion: The present study demonstrates that IGF-1 regulates the proteolytic activity of MMP-2 produced by MIO-M1 cells increasing their migratory capacity in a way that seems to be associated with IGF-1R expressed in these cells.