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SLC45A3 可作为减轻脑出血后白质损伤的潜在治疗性生物标志物。

SLC45A3 Serves as a Potential Therapeutic Biomarker to Attenuate White Matter Injury After Intracerebral Hemorrhage.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310016, China.

Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, 310016, China.

出版信息

Transl Stroke Res. 2024 Jun;15(3):556-571. doi: 10.1007/s12975-023-01145-5. Epub 2023 Mar 13.

Abstract

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.

摘要

脑出血 (ICH) 是一种严重的脑血管疾病,即使在及时的临床干预后,也会损害患者的白质。过去十年的研究表明,ICH 引起的白质损伤 (WMI) 与神经功能缺损密切相关,但其潜在机制和相关治疗仍不足。我们收集了两个数据集(GSE24265 和 GSE125512),通过对两个数据集差异表达基因进行加权基因共表达网络分析,确定了感兴趣基因的交集,确定了靶基因。单细胞 RNA-seq 分析(GSE167593)有助于定位细胞类型中的基因。此外,我们建立了由自体血或胶原酶诱导的 ICH 小鼠模型。基础医学实验和弥散张量成像用于验证 ICH 后靶基因在 WMI 中的功能。通过交集和富集分析,鉴定出 SLC45A3 为靶基因,该基因在参与脂肪酸代谢过程的少突胶质细胞分化等方面对 ICH 后的调控起着关键作用,单细胞 RNA-seq 分析也表明它主要位于少突胶质细胞中。进一步的实验验证了 SLC45A3 的过表达改善了 ICH 后的脑损伤。因此,SLC45A3 可能是 ICH 诱导的 WMI 的候选治疗性生物标志物,其过表达可能是减轻损伤的一种潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7307/11106206/f35e270aa5c5/12975_2023_1145_Fig1_HTML.jpg

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