Integrin plays a prominent role in neurite outgrowth by transmitting both mechanical and chemical signals. Integrin expression is closely associated with Astragaloside IV (AS-IV), the main component extracted from Astragali radix, which has a positive effect on neural-protection. However, the relationship between AS-IV and neurite outgrowth has not been studied exhaustively to date. The present study investigated the underlying mechanism of AS-IV on neurite outgrowth. Longer neurites have been observed in SH-SY5Y cells or cortical neurons after AS-IV treatment. Furthermore, AS-IV not only increased the expression of integrin β but also activated it. The AS-IV-induced increased integrin activity was attributed to the integrin-activating protein talin. Application of the actin force probe showed that AS-IV led to an increase in intracellular microfilament force during neurite growth. Furthermore, in response to AS-IV, the microfilament force was regulated by talin and integrin activity during neurite growth. These results suggest that AS-IV has the ability to increase intracellular structural force and facilitate neurite elongation by integrin signaling, which highlights its therapeutic potential for neurite outgrowth.
Lysine demethylase KDM7A removes histone modifications H3K9me1/2 and H3K27me1/2. KDM7A plays critical roles in gene expression and contribute to biological processes including tumorigenesis, metabolism, and embryonic development. However, the functions of KDM7A in mammalian nervous system are still poorly explored. In this study, functional roles of KDM7A are comprehensively investigated in neuronal cells by applying CUT&Tag‐seq, RNA‐seq and mice models. Knockdown of Kdm7a in N2A cells result in the alteration of histone modifications near transcription start sites (TSSs) and the expression changes of a large number of genes. In particular, the expression of immediate early genes (IEGs), a series of genes maintaining the function of the nervous system and associating with neurological disorders, are significantly decreased upon Kdm7a knockdown. Furthermore, in vivo knockdown of Kdm7a in dentate gyrus (DG) neuron of mice hippocampus, via Adeno‐associated virus (AAV)‐based stereotaxic microinjection, led to a significant decrease of the expression of c‐Fos, a marker of neuron activity. Behavior assays in mice further revealed that Kdm7a knockdown in hippocampus repress neuron activity, which leading to impairment of emotion and memory. Collectively, the study reveals that KDM7A affects neuron functions by regulating IEGs, which may provide new clues for understanding epigenetic mechanisms in neurological disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.