title: Zebularine suppresses TGF-beta-induced lens epithelial cell-myofibroblast transdifferentiation by inhibiting MeCP2.
abstract: OBJECTIVE
  Posterior capsular opacification (PCO) is a common long-term complication of modern cataract surgery. Remnant lens epithelial cells (LECs) undergo a myofibroblast transdifferentiation that is thought to be the initial step of PCO pathogenesis. The purpose of this study is to determine the effects of zebularine on transforming growth factor-β (TGFβ)-induced, LEC-myofibroblast transdifferentiation.
  
  
  METHODS
  The expression levels of methyl CpG binding protein 2 (MeCP2) and α-smooth muscle actin (α-SMA) in human PCO membranes were evaluated by confocal microscopy. The role that MeCP2 played in TGFβ2-induced α-SMA expression was analyzed by western blotting both before and after MeCP2 knockdown with MeCP2-specific siRNA. The effect of zebularine on MeCP2 expression was analyzed over time using a variety of dosages. The effect of zebularine on TGFβ2-induced α-SMA expression was determined by western blot analysis.
  
  
  RESULTS
  MeCP2 and α-SMA co-localized in human PCO membranes. When MeCP2 was depleted, TGFβ2 could not induce α-SMA expression. Zebularine decreased MeCP2 expression in lens epithelial cells in a time- and dose-dependent pattern and reversed TGFβ2-induced α-SMA expression.
  
  
  CONCLUSIONS
  MeCP2 plays an important role in TGFβ2-induced α-SMA expression in lens epithelial cells. Zebularine could reverse the TGFβ2-induced α-SMA expression by inhibiting MeCP2 expression. Therefore, zebularine could potentially prevent PCO formation.
authors: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors: Peng
authors: P
authors: Zhou
authors: Yi
authors: Y
authors: Lu
authors: Xing-Huai
authors: XH
authors: Sun
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D058442:Capsule Opacification / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002387:Cataract Extraction / Q000009:adverse effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D057852:Posterior Capsule of the Lens / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000009:adverse effects / Q000494:pharmacology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside