Glucosamine inhibits epithelial‐to‐mesenchymal transition and migration of retinal pigment epithelium cells in culture and morphologic changes in a mouse model of proliferative vitreoretinopathy |
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Authors: | Chang‐Min Liang Ming‐Cheng Tai Yun‐Hsiang Chang Yi‐Hao Chen Ching‐Long Chen Da‐Wen Lu Jiann‐Torng Chen |
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Institution: | 1. Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan;2. Department of Ophthalmology, Tri‐Service General Hospital, Taipei, Taiwan;3. Department of Ophthalmology, School of Medicine, National Defense Medical Center, Taipei, Taiwan |
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Abstract: | Purpose: To explore the effect of glucosamine (GlcN) on transforming growth factor (TGF)‐β signalling and several processes involved in proliferative vitreoretinopathy (PVR). Methods: We evaluated the surface levels of TGF‐β receptor and its binding of TGF‐β in ARPE‐19 cells. Release of cytokines and collagen, and expression of signalling intermediates were quantified. Migration was qualitatively and quantitatively examined. The morphology of cells undergoing PVR in vitro and in a mouse PVR model was observed. Results: Glucosamine reduced the surface levels of TGF‐β receptor and the ability of ARPE‐19 cells to bind TGF‐β. In ARPE‐19 cells, TGF‐β1 plus epidermal growth factor (EGF) or TGF‐β2 increased the expression of alpha‐smooth muscle actin (α‐SMA) and decreased the expression of zona occludens protein (ZO‐1). Transforming growth factor‐(β2) also caused the release of platelet‐derived growth factor (PDGF), connective tissue growth factor (CTGF) and type 1 collagen and increased the phosphorylation of SMAD2 and SMAD3. Platelet‐derived growth factor and CTGF stimulated cell migration, and TGF‐β2 stimulated wound closure, contraction of collagen and changes in cell morphology. Conclusions: Treatment with GlcN counteracted all of these effects, and its administration in the mouse model reduced the morphologic appearance of PVR. Glucosamine could inhibit the TGF‐β signalling pathway in retinal pigment epithelium cells and several of the downstream events associated with epithelial–mesenchymal transition and PVR. |
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Keywords: | epithelial‐to‐mesenchymal transition glucosamine migration proliferative vitreoretinopathy SMAD transforming growth factor‐β |
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