Abstract
Our previous study has shown that actin alpha 2 (ACTA2) is expressed in NSC and ACTA2 downregulation inhibits NSC migration by increasing RhoA expression and decreasing the expression of Rac1 to curb actin filament polymerization. Given that proliferation and differentiation are the two main characteristics of NSC, the role of ACTA2 downregulation in the proliferation and differentiation of NSC remains elusive. Here, the results demonstrated that ACTA2 downregulation using ACTA2 siRNA held the potential of inhibiting NSC proliferation using cell counting kit-8 (CCK8) and immunostaining. Then, our data illustrated that ACTA2 downregulation attenuated NSC differentiation into neurons, while directing NSC into astrocytes and oligodendrocytes using immunostaining and immunoblotting. Thereafter, the results revealed that the canonical Wnt/β-catenin pathway was involved in the effect of ACTA2 downregulation on the proliferation and differentiation of NSC through upregulating p-β-catenin and decreasing β-catenin due to inactivating GSK-3β, while this effect could be partially abolished with administration of CHIR99012, a GSK-3 inhibitor. Collectively, these results indicate that ACTA2 downregulation inhibits NSC proliferation and differentiation into neurons through inactivation of the canonical Wnt/β-catenin pathway. The aim of the present study is to elucidate the role of ACTA2 in proliferation and differentiation of NSC and to provide an intervention target for promoting NSC proliferation and properly directing NSC differentiation.
Highlights
Neural stem cells (NSC), a subtype of undifferentiated and multipotent neural cells, are available in the central nervous system (CNS) to generate three main lineages of neural cells including neurons, astrocytes, and oligodendrocytes [1,2,3]
actin alpha 2 (ACTA2) downregulation profoundly boosted the ratio of glial fibrillary acidic protein (GFAP)+ cells in group ACTA2 siRNA than group scramble (Figures 4(e) and 4(f)). These results revealed that ACTA2 downregulation inhibited NSC differentiation into the neurons, while directing NSC differentiation into glial lineages including astrocytes and oligodendrocytes
The results indicated that the expression of GSK-3β showed no prominent difference among these four groups (Figure 5(a)), while the expression of p-GSK-3β in group ACTA2 siRNA was significantly reduced, compared to the other three groups (Figures 5(a) β-III-Tubulin/GAPDH
Summary
Neural stem cells (NSC), a subtype of undifferentiated and multipotent neural cells, are available in the central nervous system (CNS) to generate three main lineages of neural cells including neurons, astrocytes, and oligodendrocytes [1,2,3]. The adult NSC are proliferated in SVZ and migrated towards lesions to exert multiple neurorestorative effects after brain injury [4]. These neurorestorative effects including but not limited to cell replacement, neuromodulation, and neurotrophic support to accelerate functional recovery in various. The vast majority of NSC originated from SVZ differentiate into astrocytes to generate glial scars after central neuropathy [13,14,15]. Exploring approaches to direct NSC differentiation into neurons, instead of astrocytes, might be a viable avenue to broaden the application of NSC for the treatment of CNS insults
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