Topoisomerase IIα-mediated stemness response in reactive astrocytes to traumatic brain injury.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-04-13 eCollection Date: 2025-01-01 DOI:10.7150/thno.111923
Shangyao Qin, Xiao Huang, Yimin Yuan, Hong Liu, Jiali Li, Ziwei Dai, Zhida Lan, Yingyan Pu, Cheng He, Zhida Su
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引用次数: 0

Abstract

Rationale: As a highly plastic population, parenchymal astrocytes have demonstrated the capacity to become activated and recapitulate neurogenic potential in response to traumatic central nervous system (CNS) injuries, representing a latent reservoir for neuronal regeneration in non-neurogenic brain regions. However, the extrinsic and intrinsic factors regulating this process remain poorly characterized. Elucidating these molecular mechanisms is crucial to harnessing the regenerative potential of reactive astrocytes in CNS repair. Methods: A multidisciplinary approach combining immunostaining, western blotting, RNA interference (RNAi), gene knock out and fate-mapping was used to investigate the role of topoisomerase IIα (TOP2a) in regulation of the stemness response in reactive astrocytes to traumatic brain injury (TBI). Results: Both in vitro and in vivo analyses demonstrated that TBI induces a stem cell-like response in reactive astrocytes concomitant with TOP2a upregulation. Pharmacological inhibition or genetic deletion of TOP2a significantly attenuated this stemness response. Neurosphere culture assay indicates that TOP2a might act as a downstream factor of Sonic Hedgehog (SHH) signaling to mediate the acquisition of stem cell potential. Conclusions: This study identifies TOP2a as a pivotal intrinsic regulator of astrocytic stem cell potential in the injured brain, which will advance our understanding of the molecular underpinnings of the stem cell response and its therapeutic application in neural regeneration.

拓扑异构酶ii α-介导的星形胶质细胞对创伤性脑损伤的干性反应。
理由:作为一个高度可塑性的群体,实质星形胶质细胞已经被证明有能力被激活,并在中枢神经系统(CNS)创伤后重现神经源性电位,代表了非神经源性脑区域神经元再生的潜在储存库。然而,调节这一过程的外在因素和内在因素仍然缺乏特征。阐明这些分子机制对于在中枢神经系统修复中利用反应性星形胶质细胞的再生潜力至关重要。方法:采用免疫染色、western blotting、RNA干扰(RNAi)、基因敲除和命运定位相结合的多学科方法,研究拓扑异构酶i α (TOP2a)在反应性星形胶质细胞对创伤性脑损伤(TBI)干性反应中的调控作用。结果:体外和体内分析均表明,TBI可诱导反应性星形胶质细胞的干细胞样反应,同时TOP2a上调。药理抑制或基因缺失的TOP2a显著减弱了这种干性反应。神经球培养实验表明,TOP2a可能作为Sonic Hedgehog (SHH)信号的下游因子介导干细胞潜能的获得。结论:本研究确定了TOP2a是脑损伤星形细胞干细胞电位的关键内在调节因子,这将促进我们对干细胞反应的分子基础及其在神经再生中的治疗应用的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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