高速率机械刺激改变了3D水凝胶中少突胶质前体细胞的增殖和成熟相关信号

Ryosuke Yokosawa , Rachel A. Mazur , Kelsey A. Wilson , Jacob H. Lee , Noah W. Showalter , Kyle J. Lampe , Pamela J. VandeVord
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摘要

创伤性脑损伤(TBI)可导致神经炎症,并与慢性神经变性有关。许多TBI研究旨在进一步了解脑细胞对与TBI相关的机械力作出反应的机制。其中,轻度TBI是TBI患者中最常见的损伤级别,神经胶质细胞的反应性是理解轻度TBI的关键机制。然而,关于少突胶质前体细胞(OPCs)的研究却很少。OPCs通过迁移、增殖和分化成少突胶质细胞(OL)来响应损伤,以协助损伤后的修复。鉴于其增殖和分化的能力,OPCs是OL再生的一个有希望的治疗靶点。尽管OPCs在维持正常神经元功能方面发挥着重要作用,但对机械性损伤的反应仍然知之甚少。因此,本研究旨在利用一个模拟脑组织的体外3D水凝胶平台来阐明OPCs的细胞反应,以确定驱动其反应的关键信号通路。在这项研究中,我们对OPCs施加高速率压力波诱导轻度TBI,并通过量化细胞生长、代谢活性、基因和蛋白质表达来评估随后的细胞和分子反应。尽管高速率机械损伤没有显著影响细胞存活,但它诱导了与OPC增殖和成熟相关的分子靶点的转录组学和蛋白质组学变化,包括PDGFRA、GALC、CTNNB1和HSP90AB。这些失调和改变的分子谱为OPC损伤反应提供了有价值的见解,并可能作为治疗神经退行性疾病的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

High-rate mechano-stimulation alters proliferation- and maturation-related signaling of oligodendrocyte precursor cells in a 3D hydrogel

High-rate mechano-stimulation alters proliferation- and maturation-related signaling of oligodendrocyte precursor cells in a 3D hydrogel
Traumatic brain injury (TBI) leads to neuroinflammation and is associated with chronic neurodegeneration. Many TBI studies aim to understand further the mechanism by which cells in the brain respond to the mechanical forces associated with TBI. In particular, mild TBI is the most common level of injury among TBI patients, and the reactivity of glial cells is a key mechanism in understanding mild TBI. However, there is a lack of studies focusing on oligodendrocyte precursor cells (OPCs). OPCs respond to the injury by migration, proliferation, and differentiation into oligodendrocytes (OL) to assist in post-injury repair. Given their ability to proliferate and differentiate, OPCs are a promising therapeutic target for OL regeneration. Despite their important role in maintaining normal neuronal functions, the response of OPCs to mechanical insult remains poorly understood. Thus, this study aims to elucidate the cellular responses of OPCs using a brain-tissue mimicking in vitro 3D hydrogel platform to identify key signaling pathways driving their response. In this study, we applied a high-rate pressure wave to OPCs to induce mild TBI and assess subsequent cellular and molecular responses by quantifying cell growth, metabolic activity, and gene and protein expression. Although the high-rate mechanical insult did not significantly impact cell survival, it induced transcriptomic and proteomic changes in molecular targets related to OPC proliferation and maturation, including PDGFRA, GALC, CTNNB1, and HSP90AB. These dysregulations and altered molecular profiles provide valuable insights into the OPC injury response and may serve as potential therapeutic targets for treating neurodegeneration.
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