Sodium iodate influences the apoptosis, proliferation and differentiation potential of radial glial cells in vitro.

Abstract

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.

• Authors: Xi Chen, Qiyou Li, Haiwei Xu, Zheng Qin Yin
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 34 Issue 4 Pg. 1109-24 ( 2014) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25277056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Bone Morphogenetic Protein 4
• Carrier Proteins
• Iodates
• Smad2 Protein
• Smad3 Protein
• Transforming Growth Factor beta1
• Tubulin
• beta Catenin
• noggin protein
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Glycogen Synthase Kinase 3
• sodium iodate

Topics

• Animals
• Apoptosis (drug effects)
• Bone Morphogenetic Protein 4 (metabolism)
• Carrier Proteins (metabolism)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Ependymoglial Cells (drug effects, metabolism)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• In Vitro Techniques
• Iodates (pharmacology)
• Mice
• Signal Transduction (drug effects)
• Smad2 Protein (metabolism)
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Tubulin (metabolism)
• Wnt Signaling Pathway (drug effects)
• beta Catenin (metabolism)