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基于 iTRAQ 的定量蛋白质组学分析小鼠肝部分切除术后肝再生终止期的肝脏。

iTRAQ-based quantitative proteomic analysis of the liver regeneration termination phase after partial hepatectomy in mice.

机构信息

Core Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China.

General surgery Department, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China.

出版信息

J Proteomics. 2022 Sep 15;267:104688. doi: 10.1016/j.jprot.2022.104688. Epub 2022 Jul 29.

Abstract

Liver regeneration (LR) is an important biological process after liver injury. As the "brake" in the process of LR, the termination phase of LR not only suppresses the continuous increase in liver volume but also effectively promotes the recovery of liver function. However, the mechanisms underlying the termination phase of LR are still not clear. In our study, we used isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis to determine the protein expression profiles of livers in the termination phase of mouse LR after partial hepatectomy (PH). We found that the expression of 197 proteins increased gradually during LR; in addition, 187 proteins were upregulated and 264 proteins were downregulated specifically in the termination phase of LR. The GO analysis of the proteins revealed the upregulation of "cell-cell adhesion" and "translation" and the downregulation of the "oxidation-reduction process". The KEGG pathway analysis showed that "biosynthesis of antibiotics" and "ribosomes" were significantly upregulated, while "metabolic pathways" were significantly downregulated. These analyses indicated that the termination phase of LR mainly focuses on restoring cellular structure and function. Differentially expressed proteins such as SNX5 were also screened out from biological processes. SIGNIFICANCE: The key regulatory factors in the termination phase of LR were studied by iTRAQ-based proteomics to lay a foundation for further study of the molecular mechanism and biomarkers of the termination phase of LR. This study will guide the clinical perioperative management of patients after hepatectomy.

摘要

肝再生(LR)是肝损伤后重要的生物学过程。作为 LR 过程中的“刹车”,LR 的终止阶段不仅抑制肝体积的持续增加,而且有效促进肝功能的恢复。然而,LR 终止阶段的机制尚不清楚。在我们的研究中,我们使用基于等重标记相对和绝对定量(iTRAQ)的定量蛋白质组学分析方法,确定了部分肝切除(PH)后小鼠 LR 终止阶段肝脏的蛋白质表达谱。我们发现,在 LR 过程中,197 种蛋白质的表达逐渐增加;此外,LR 终止阶段有 187 种蛋白质上调,264 种蛋白质下调。蛋白质的 GO 分析显示“细胞-细胞黏附”和“翻译”上调,“氧化还原过程”下调。KEGG 途径分析表明“抗生素的生物合成”和“核糖体”显著上调,而“代谢途径”显著下调。这些分析表明,LR 终止阶段主要集中在恢复细胞结构和功能上。从生物过程中还筛选出了差异表达蛋白,如 SNX5。意义:通过 iTRAQ 蛋白质组学研究 LR 终止阶段的关键调控因子,为进一步研究 LR 终止阶段的分子机制和生物标志物奠定基础。这项研究将指导肝切除术后患者的临床围手术期管理。

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