Activated alpha-2 macroglobulin induces M¨¹ller glial cell migration by

BARCELONA PF; JALDIN-FINCATI J; SANCHEZ MC; CHIABRANDO GA

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2013

0892-6638

n retinal proliferative diseases, Müller glial cells (MGC) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloprotease-2 (MMP-2) and MMP-9 also present increased levels of the protease inhibitor α2-macroglobulin (α2M) and its receptor the low density lipoprotein receptor-related protein 1 (LRP1). In the present work, we investigated whether the protease activated form of α2M, α2M*, and LRP1 are involved with the MGC migratory process. By performing wound-scratch migration and zymography assays, we demonstrated that α2M* induced cell migration and proMMP-2 activation in the human Müller glial cell line MIO-M1. This induction was blocked when LRP1 and MT1-MMP were knocked down with siRNA techniques. Using fluorescence microscopy and biochemical procedures we found that α2M* induced an increase in LRP1 a