title: 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.
abstract: OBJECTIVE
  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.
authors: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors: Chang-Min
authors: CM
authors: Liang
authors: Ming-Cheng
authors: MC
authors: Tai
authors: Yun-Hsiang
authors: YH
authors: Chang
authors: Yi-Hao
authors: YH
authors: Chen
authors: Ching-Long
authors: CL
authors: Chen
authors: Da-Wen
authors: DW
authors: Lu
authors: Jiann-Torng
authors: JT
authors: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000502:physiology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D062826:Zonula Occludens-1 Protein
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D016207:Cytokines; D008565:Membrane Proteins; D010750:Phosphoproteins; D018125:Receptors, Transforming Growth Factor beta; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D016212:Transforming Growth Factor beta; D062826:Zonula Occludens-1 Protein; D003094:Collagen; D005944:Glucosamine