M¨¹ller cells (MC) are known to promote cellular migration during retinal proliferative diseases, which involve matrix metalloproteinases (MMPs) production. In previous studies we have demonstrated that MC express LDL receptor-related protein 1 (LRP1), and its ligand alpha 2-macroglobulin (¦Á2M) is able to induce MMP-2 activity, suggesting that ¦Á2M/LRP1 system is implicated in cell migration during these retinal disorders. However, the biochemical mechanisms by which ¦Á2M/LRP1 system control this cellular event is, at present, unknown. Herein, we investigate the putative mechanism of ¦Á2M/LRP1 system on the MMPs regulation and MC migration using the human MIO-M1 cell line. Cell migration was determined by wound-healing assay. MIO-M1 cells were seeded in laminin- or collagen-coated dishes, and after 18 h of quiescence, a wound was created across the surface with a tip. The cells that move into the scraped area were quantified by light microscopy. ¦Á2M-induced cell migration was increased on laminin- and collagen-matrix substrate respect to control. These results were associated with the effects of ¦Á2M on: i) intracellular signal activation; ii) increased MMP-2 activity; and iii) expression and membrane focal localization of MT1-MMP and TIMP-2. Our data, taken togheter, demonstrate that ¦Á2M/LRP1 system is implicated in M¨¹ller Glial cell migration.
