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9-cis-Retinoic Acid and 1,25-dihydroxy Vitamin D3 Improve the Differentiation of Neural Stem Cells into Oligodendrocytes through the Inhibition of the Notch and Wnt Signaling Pathways | ||
Iranian Journal of Medical Sciences | ||
مقاله 9، دوره 43، شماره 5، آذر 2018، صفحه 523-532 اصل مقاله (1.08 M) | ||
نوع مقاله: Original Article(s) | ||
شناسه دیجیتال (DOI): 10.30476/ijms.2018.40573 | ||
نویسندگان | ||
Saeedeh Saeb1؛ Hassan Azari2؛ Zohreh Mostafavi-Pour1؛ Amir Ghanbari3؛ Sepideh Ebrahimi1؛ Pooneh Mokarram* 1 | ||
1Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran; | ||
2Neural Stem Cell and Regenerative Neuroscience Laboratory, Department of Anatomical Sciences and Shiraz Stem Cell Institute, Shiraz University of Medical Sciences, Shiraz, Iran | ||
3Department of Anatomical Sciences, Yasuj University of Medical sciences, Yasuj, Iran | ||
چکیده | ||
Background: Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways.Methods: Cortical neural stem cells were isolated from 14-day-old rat embryos and cultured using the neurosphere assay. The cells were treated in 4 different conditions for 1 week: the negative control group received only the basic fibroblast growth factor, the positive control group received only T3 without growth factors, the RA group was treated with 9-cis-RA, and the Vit D3 group was treated with 1,25(OH)2D3. The effects of 9-cis-RA and 1,25(OH)2D3 on the level of the myelin basic protein (MBP) and the gene expression of the SOX10, MBP gene, HES5, and LRP6 were studied using flow cytometry and real-time PCR. The data were analyzed using one-way ANOVA with GraphPad Prism. A P value less than 0.05 was considered significant. Results: The mRNA expressions of the SOX10, MBP, and MBP gene were significantly increased in the treated groups compared with the negative control group; the increase was similar in the 9-cis-RA group and the positive control group. Furthermore, 9-cis-RA significantly decreased the expression of the HES5 gene, a Notch signaling pathway transcription factor, and 1,25(OH)2D3 significantly reduced the expression of the LRP6 gene, a Wnt signaling pathway co-receptor. Conclusion: It seems that 9-cis-RA and 1,25(OH)2D3 are good candidates to improve the differentiation of OPCs into oligodendrocytes. | ||
کلیدواژهها | ||
Cell differentiation؛ Oligodendrocyte precursor cells؛ 9-cis-retinoic acid؛ 1,25-dihydroxy vitamin D3؛ Receptors, Wnt؛ Notch signaling pathway | ||
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