Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation.

Ji Zhang,Chao Zhang,Huanhuan Li,Xuanyu Fang,Quan Hu,Anyong Yu,Xuheng Jiang,Jun Zhong,Fangke Xie,Xiaojun Zhang,Hongfei Ge,Xiaofei Huang

doi:10.1155/2020/4764012

Abstract

Although neural stem cells (NSCs) could migrate towards lesions after central nervous system (CNS) injury, the migration ability always is restricted due to the disturbed composition and density of the adhesion ligands and extracellular matrix (ECM) gradient after CNS injury. To date, various methods have been developed to enhance NSC migration and a number of factors, which are affecting NSC migration potential, have been identified. Here, primary NSCs were cultured and the expression of actin alpha 2 (ACTA2) in NSCs was determined using reverse transcription polymerase chain reaction (RT-PCR) and immunostaining. Next, the role of ACTA2 in regulating NSC migration and the potential mechanism was explored. Our results demonstrated that ACTA2 expressed in NSCs. Meanwhile, downregulated ACTA2 using siRNA inhibited NSC migration through hindering actin filament polymerization via increasing RhoA expression and decreasing Rac1 expression. The present study might enrich the basic knowledge of ACTA2 in NSC migration and open an avenue for enhancing NSC migration potential, subsequently providing an intervention target for functional recovery after CNS injury.

Highlights

Stem cells (SCs) are a subtype of unspecialized cells with the capacity of self-renewal and differentiation into one or more developmental cell linage(s) and have aroused great attention for tissue regeneration [1]
A previous study has indicated that Neural stem cells (NSCs) could proliferate in the subventricular zone (SVZ), one region of the adult brain that persists neurogenesis throughout adult life [4], but only a small number of proliferated NSCs migrate to the lesions after ischemic stroke [5], suggesting that limited functional recovery might be due to insufficient functional NSCs in lesions
The aim of this study is to look for factors influencing NSC migration and elucidate the possible underlying mechanism(s), which might enrich the basic theory related to NSCs and provide an intervention target for enhancing NSC migration potential, promoting functional recovery after various neurological diseases and injuries

Summary

Introduction

Stem cells (SCs) are a subtype of unspecialized cells with the capacity of self-renewal and differentiation into one or more developmental cell linage(s) and have aroused great attention for tissue regeneration [1]. Neural stem cells (NSCs) could be activated, de novo proliferated, migrated towards the lesions, directed to three major central nervous system (CNS) cell type: neurons, astrocytes, and oligodendrocytes, and integrated into the injured regions to regulate tissue homeostasis and repair after CNS injury [1,2,3]. Cell migration relies on actin filament polymerization at the leading edge. NSCs are one of the most common motile cell subtypes. Our previous study has indicated that α-actinin 4 (ACTN4) promotes actin filament polymerization and enhances NSC migration [1]. Our study indicates that CDC42 activation facilitates NSC movement through promoting actin filament polymerization [3]. Molecules affecting actin filament polymerization of NSCs might direct NSC motility

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