SLC45A3 是减轻脑出血后白质损伤的潜在治疗生物标记物

IF 3.8 2区 医学 Q1 CLINICAL NEUROLOGY Translational Stroke Research Pub Date : 2024-06-01 Epub Date: 2023-03-13 DOI:10.1007/s12975-023-01145-5
Yi Zhang, Hanhai Zeng, Feiyang Lou, Xiaoxiao Tan, Xiaotong Zhang, Gao Chen
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引用次数: 0

摘要

脑出血(ICH)是一种严重的脑血管疾病,即使经过及时的临床干预,患者的脑白质仍会受损。近十年来的研究表明,ICH 引起的脑白质损伤(WMI)与神经功能缺损密切相关,但其潜在机制和相关治疗方法尚不充分。我们收集了两个数据集(GSE24265 和 GSE125512),通过加权基因共表达网络分析发现的有趣基因之间的交集,确定了两个数据集中差异表达基因后的靶基因。额外的单细胞 RNA-seq分析(GSE167593)帮助我们确定了该基因在细胞类型中的位置。此外,我们还建立了由自体血或胶原酶诱导的 ICH 小鼠模型。应用基础医学实验和弥散张量成像来验证目标基因在 ICH 后 WMI 中的功能。通过交叉和富集分析,SLC45A3基因被确定为靶基因,该基因在ICH后少突胶质细胞分化调控中起关键作用,参与脂肪酸代谢过程等,单细胞RNA-seq分析也表明该基因主要定位于少突胶质细胞。进一步的实验证实,过表达 SLC45A3 可改善 ICH 后的脑损伤。因此,SLC45A3 可作为 ICH 诱导的 WMI 的候选治疗生物标志物,而过表达它可能是减轻损伤的一种潜在方法。
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SLC45A3 Serves as a Potential Therapeutic Biomarker to Attenuate White Matter Injury After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease, which impairs patients' white matter even after timely clinical interventions. Indicated by studies in the past decade, ICH-induced white matter injury (WMI) is closely related to neurological deficits; however, its underlying mechanism and pertinent treatment are yet insufficient. We gathered two datasets (GSE24265 and GSE125512), and by taking an intersection among interesting genes identified by weighted gene co-expression networks analysis, we determined target genes after differentially expressing genes in two datasets. Additional single-cell RNA-seq analysis (GSE167593) helped locate the gene in cell types. Furthermore, we established ICH mice models induced by autologous blood or collagenase. Basic medical experiments and diffusion tensor imaging were applied to verify the function of target genes in WMI after ICH. Through intersection and enrichment analysis, gene SLC45A3 was identified as the target one, which plays a key role in the regulation of oligodendrocyte differentiation involving in fatty acid metabolic process, etc. after ICH, and single-cell RNA-seq analysis also shows that it mainly locates in oligodendrocytes. Further experiments verified overexpression of SLC45A3 ameliorated brain injury after ICH. Therefore, SLC45A3 might serve as a candidate therapeutic biomarker for ICH-induced WMI, and overexpression of it may be a potential approach for injury attenuation.

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来源期刊
Translational Stroke Research
Translational Stroke Research CLINICAL NEUROLOGY-NEUROSCIENCES
CiteScore
13.80
自引率
4.30%
发文量
130
审稿时长
6-12 weeks
期刊介绍: Translational Stroke Research covers basic, translational, and clinical studies. The Journal emphasizes novel approaches to help both to understand clinical phenomenon through basic science tools, and to translate basic science discoveries into the development of new strategies for the prevention, assessment, treatment, and enhancement of central nervous system repair after stroke and other forms of neurotrauma. Translational Stroke Research focuses on translational research and is relevant to both basic scientists and physicians, including but not restricted to neuroscientists, vascular biologists, neurologists, neuroimagers, and neurosurgeons.
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