S100a4 promotes differentiation of neural stem cells through up-regulation of brain-derived neurotrophic factor / 中国组织工程研究

ABSTRACT

BACKGROUND: How to promote neural stem cells differentiate into neurons is a difficulty. S100A4 has been found to play a role in the nervous system repair by various pathways. OBJECTIVE: To investigate whether S100A4 affects the differentiation of neural stem cells into neurons through up-regulating the expression of brain-derived neurotrophic facto. METHODS: The neural stem cells from brain hippocampus and subependymal region of embryonic mice were cultured in vitro and passaged. The S100A4 expression vector and/or brain-derived neurotrophic factor + siRNA were transfected into neural stem cells by electroporation, and the cells were induced to differentiate into neurons at 48 hours after transfection. Three days later, the expression levels of brain-derived neurotrophic factor and Tuj1 in cells were detected by western blot assay. Proportion of Tuj1 positive neurons was tested by immunofluorescence. RESULTS AND CONCLUSION: Compared with the unrelated sequence plasmid group, the proportion of Tuj1 positive neurons and the expression levels of Tuj1 and brain-derived neurotrophic factor in the S100A4 transfection group were significantly increased (P < 0.01). Compared with the S100A4+siRNA unrelated sequence plasmid group, the proportion of Tuj1 positive neurons and the expression levels of Tuj1 and brain-derived neurotrophic factor in the co-transfection group were significantly decreased (P < 0.01). These results indicate that S100A4 overexpression can promote the differentiation of neural stem cells into neurons, which may be mediated by brain-derived neurotrophic factor.