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Pablo F. Barcelona, Susana G. Ortiz, Gustavo A. Chiabrando, Maria C. Sánchez; α2-Macroglobulin Induces Glial Fibrillary Acidic Protein Expression Mediated by Low-Density Lipoprotein Receptor-Related Protein 1 in Müller Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(2):778-786. doi: 10.1167/iovs.10-5759.
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Although it is known that Müller cells express the glial fibrillary acidic protein (GFAP) in response to acute retinal damage, the regulatory mechanism is not completely understood. α2-Macroglobulin (α2M) and its receptor, low-density lipoprotein receptor-related protein 1 (LRP1), have also been found in injured retinas. Herein, the authors examined the involvement of the α2M/LRP1 system in GFAP expression in Müller cells using in vitro and in vivo experimental models.
Using Western blot analysis and immunocytochemistry, the authors evaluated the effect of α2M* on GFAP expression in the Müller cell line MIO-M1, which constitutively expresses LRP1. Intracellular signaling pathways activated by α2M* were examined by Western blot analysis. The effect of α2M* on GFAP expression in the mouse retina was examined by intravitreal microinjection of α2M* in mouse eyes.
These data demonstrate that α2M* induced GFAP expression in the MIO-M1 cell line, which was selectively blocked by RAP, an antagonist of LRP1 binding ligands. In addition, α2M* induced JAK/STAT pathway activation, determined by STAT3 phosphorylation (p-STAT3), which was also blocked by RAP. Finally, the authors showed that GFAP was expressed in the retinas of mice, preferentially in Müller cells at 3 and 6 days after a single intravitreal α2M* injection, whereas p-STAT3 staining increased at day 1 in both the ganglion cell layer and the inner nuclear layer.
These results demonstrate that α2M* induces GFAP expression in retinal Müller cells through LRP1, which could be mediated by JAK/STAT pathway activation.
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