title: Sodium iodate influences the apoptosis, proliferation and differentiation potential of radial glial cells in vitro.
abstract: OBJECTIVE
  Sodium iodate (NaIO3)-induced acute retinal injury is typically used as an animal model for degenerative retinal disease; however, how NaIO3 influences the apoptosis, proliferation and differentiation of endogenous retinal stem cells is unknown.
  
  
  METHODS
  We exposed a radial glial cells (RGCs) line (L2.3) to different NaIO3 concentrations and determined the influence of NaIO3 on apoptosis, proliferation, and differentiation using flow cytometry and immunofluorescence assays. We used a real-time polymerase chain reaction assay to analyze the levels of mRNAs encoding GSK-3β, AXIN2, β-catenin, TGF-β1, SMAD2, SMAD3, NOG (Noggin), and BMP4.
  
  
  RESULTS
  Cell density decreased dramatically as a function of the NaIO3 dose. NaIO3 increased apoptosis, inhibited mitosis, proliferation, and the Wnt/β-catenin pathway. CHIR99021 (Wnt agonist) treatment efficiently reversed the effects of NaIO3 on the apoptosis and proliferation of RGCs. The number of neuronal class III β-tubulin-positive cells decreased markedly, whereas that of glial fibrillary acidic protein-positive cells increased significantly when RGCs were exposed to NaIO3. During differentiation, the Nog mRNA level decreased and transforming growth factor-β1 (Tgf-β1) and Smad2/3 mRNA levels increased significantly when RGCs were exposed to NaIO3.
  
  
  CONCLUSIONS
  NaIO3 increased apoptosis, influenced the proliferation of RGCs and drove them toward astrocytic differentiation, likely through inhibition of the Wnt/β-catenin and noggin pathways and activation of the TGF-β1/SMAD2/3 pathway.
authors.affiliation: Department of Ophthalmology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Qiyou
authors.initials: Q
authors.lastname: Li
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
authors.forename: Zheng Qin
authors.initials: ZQ
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D063928:Ependymoglial Cells / Q000187:drug effects* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D066298:In Vitro Techniques; D007452:Iodates / Q000494:pharmacology*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007452:Iodates; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D014404:Tubulin; D051176:beta Catenin; D000099176:Noggin Protein; C000605507:Gsk3b protein, mouse; C032285:sodium iodate