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GA Limb, SE Moss, G Murphy, PT Khaw; Relationship Between Müller Cell Expression of MMP-1 and Cell Cycle Progression . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4519.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Pathological changes in the neural retina invariably lead to Müller cell proliferation, migration and differentiation, a process known as reactive gliosis. Since matrix metalloproteinases are known to play an important role in these cellular activities, we investigated the expression of matrix metalloproteinase 1 (MMP-1) by the spontaneously immortalized Müller cell line MIO-M1, and examined the relationship between the expression of this enzyme and cell cycle progression. Methods: Müller cell cultures were synchronized in M-phase with Nocodazole for 18 hours, and cell cycle status and expression of MMP-1 were examined by western blotting and confocal microscopy analysis, using various monoclonal and polyclonal antibodies to MMP-1, and polyclonal antibodies to cell cycle proteins. Whole cell lysates and nuclear and cytoplasmic extracts, prepared at various times after Nocodazole release, were also investigated for the expression of these molecules. Results: The results showed that retinal Müller cells in culture stain for MMP-1, and that the intensity of staining for this enzyme is related to cell cycle progression. Although both cytoplasmic and nuclear staining for MMP-1 were observed throughout culture, a strong nuclear staining for this molecule was observed at 6 and 24 hours after Nocodazole release, the time when cyclin B and Cdc2 were expressed at their highest levels by these cells. Western blot analysis of nuclear and cytoplasmic lysates showed that MMP-1 preferentially accumulates in the nuclei of Müller cells during the M-phase of the cell cycle. Conclusion: These observations indicate that MMP-1 is strongly expressed by Müller cells, and suggest that this matrix degrading enzyme may play an important role in the control of Müller cell proliferation and differentiation during retinal proliferative disease.
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