The up-regulation of glial fibrillary acidic protein (GFAP), an intermediate filament protein (IF), is an indicator of ¡®¡®stress¡¯¡¯ in M¨¹ller cells (MC) during proliferative retinal diseases. Previously, we have demonstrated an increased expression of alpha-2 macroglobulin (¦Á2M) in the vitreous of human subjects with proliferative diabetic retinopathy (PDR) as well as in retinas of rats with ischemia-induced neovascularization. In this animal model, the ¦Á2M receptor, LRP1, showed a high level of protein expression like to GFAP, in MC. However, the functional significance between ¦Á2M/LRP1 system and GFAP is, at the present, unknown. Herein, we investigate the effect of ¦Á2M on the GFAP expression in a human M¨¹ller cell line, MIO-M1, which express LRP1. The GFAP expression was determined by Westen blot and immunofluorescence microscopy. We demonstrated that the ¦Á2M/LRP1 interaction induced GFAP expression in MIO-M1 cell line. This expression was significantly blocked by RAP, an antagonist of LRP1-binding ligands. However, vimentin, another IF, showed an uniform pattern of expression which was not modified by the ¦Á2M stimulation. In conclusion, our results demonstrate that ¦Á2M/LRP1 system promotes a differential IF regulation in MC with a preferential GFAP up-regulation, which suggests that ¦Á2M/LRP1 system play a key role in neuroprotective events occurred in retinal disorders as PDR.
