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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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© 2017 Association for Research in Vision and Ophthalmology.
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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