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基于 trkB.T1 敲除小鼠脊髓组织基因表达谱鉴定与脊髓损伤相关的关键基因。

Identification of critical genes associated with spinal cord injury based on the gene expression profile of spinal cord tissues from trkB.T1 knockout mice.

机构信息

Department of Rehabilitation, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.

出版信息

Mol Med Rep. 2019 Mar;19(3):2013-2020. doi: 10.3892/mmr.2019.9884. Epub 2019 Jan 22.

Abstract

The present study aimed to identify the genes and underlying mechanisms critical to the pathology of spinal cord injury (SCI). Gene expression profiles of spinal cord tissues of trkB.T1 knockout (KO) mice following SCI were accessible from the Gene Expression Omnibus database. Compared with trkB.T1 wild type (WT) mice, the differentially expressed genes (DEGs) in trkB.T1 KO mice following injury at different time points were screened out. The significant DEGs were subjected to function, co‑expression and protein‑protein interaction (PPI) network analyses. A total of 664 DEGs in the sham group and SCI groups at days 1, 3, and 7 following injury were identified. Construction of a Venn diagram revealed the overlap of several DEGs in trkB.T1 KO mice under different conditions. In total, four modules (Magenta, Purple, Brown and Blue) in a co‑expression network were found to be significant. Protein tyrosine phosphatase, receptor type C (PTPRC), coagulation factor II, thrombin (F2), and plasminogen (PLG) were the most significant nodes in the PPI network. 'Fc γ R‑mediated phagocytosis' and 'complement and coagulation cascades' were the significant pathways enriched by genes in the PPI and co‑expression networks. The results of the present study identified PTPRC, F2 and PLG as potential targets for SCI treatment, which may further improve the general understanding of SCI pathology.

摘要

本研究旨在鉴定与脊髓损伤 (SCI) 病理学相关的关键基因和潜在机制。可从基因表达综合数据库中获得 trkB.T1 敲除 (KO) 小鼠 SCI 后脊髓组织的基因表达谱。与 trkB.T1 野生型 (WT) 小鼠相比,筛选出损伤后不同时间点 trkB.T1 KO 小鼠中差异表达的基因 (DEGs)。对显著的 DEGs 进行功能、共表达和蛋白质-蛋白质相互作用 (PPI) 网络分析。在假手术组和 SCI 组的 1、3 和 7 天损伤后,鉴定出 664 个 DEGs。构建 Venn 图显示了不同条件下 trkB.T1 KO 小鼠中几个 DEG 的重叠。总共在共表达网络中发现了四个模块 (Magenta、Purple、Brown 和 Blue)。蛋白酪氨酸磷酸酶,受体型 C (PTPRC)、凝血因子 II、凝血酶 (F2) 和纤溶酶原 (PLG) 是 PPI 网络中最重要的节点。PPI 和共表达网络中基因富集的显著途径包括“FcγR 介导的吞噬作用”和“补体和凝血级联反应”。本研究的结果确定了 PTPRC、F2 和 PLG 作为 SCI 治疗的潜在靶点,这可能进一步提高对 SCI 病理学的总体认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69a1/6390051/50043a1a4bcf/MMR-19-03-2013-g00.jpg

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