Sodium Iodate Influences the Apoptosis, Proliferation and Differentiation Potential of Radial Glial Cells In Vitro

Cellular Physiology and Biochemistry

关键词: TGF-β1;    Wnt/β-catenin;    Differentiation;    Radial glial cells;    Proliferation;    Sodium iodate;   

DOI  :  10.1159/000366325

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims 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. Conclusion 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.

【 授权许可】

CC BY-NC-ND