肝蛋白质组学分析揭示了宿主对脓毒症免疫反应中涉及的关键蛋白。
Liver proteomic analysis reveals the key proteins involved in host immune response to sepsis.
机构信息
Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.
Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
出版信息
PeerJ. 2023 May 26;11:e15294. doi: 10.7717/peerj.15294. eCollection 2023.
BACKGROUND
Sepsis is a serious infection-induced response in the host, which can result in life-threatening organ dysfunction. It is of great importance to unravel the relationship between sepsis and host immune response and its mechanisms of action. Liver is one of the most vulnerable organs in sepsis, however, the specific pathogenesis of septic liver injury has not been well understood at the protein level.
METHODS
A total of 12 healthy Sprague-Dawley (SD) male rats aged from 6 to 8 weeks were adaptively housed in individual cages in the specific pathogen free animal room. These lab rats were grouped into two groups: treatment ( = 9) and control ( = 3) groups; only three mice from the treatment group survived and were used for subsequent experiments. A TMT-based proteomic analysis for liver tissue was performed in the septic rat model.
RESULTS
A total of 37,012 unique peptides were identified, and then 6,166 proteins were determined, among which 5,701 were quantifiable. Compared to the healthy control group, the septic rat group exhibited 162 upregulated and 103 downregulated differentially expressed proteins (DEPs). The upregulated and downregulated DEPs were the most significantly enriched into the complement and coagulation cascades and metabolic pathways. Protein-protein interaction (PPI) analysis further revealed that the upregulated and downregulated DEPs each clustered in a PPI network. Several highly connected upregulated and downregulated DEPs were also enriched into the complement and coagulation cascades pathways and metabolic pathways, respectively. The parallel reaction monitoring (PRM) results of the selected DEPs were consistent with the results of the TMT analysis, supporting the proteomic data.
CONCLUSION
Our findings highlight the roles of complement and coagulation cascades and metabolic pathways that may play vital roles in the host immune response. The DEPs may serve as clinically potential treatment targets for septic liver injury.
背景
脓毒症是宿主发生严重感染后的全身性反应，可能导致危及生命的器官功能障碍。深入了解脓毒症与宿主免疫反应的关系及其作用机制非常重要。肝脏是脓毒症中最易受损的器官之一，但脓毒性肝损伤的具体发病机制在蛋白质水平上尚未得到很好的理解。
方法
将 12 只 6 至 8 周龄的健康雄性 Sprague-Dawley（SD）大鼠单独饲养在无特定病原体的动物房中，适应性饲养。将这些实验大鼠分为两组：治疗组（n=9）和对照组（n=3）；只有治疗组的 3 只大鼠存活下来，用于后续实验。对脓毒症大鼠模型的肝组织进行了 TMT 基于的蛋白质组学分析。
结果
共鉴定到 37012 个独特肽段，确定了 6166 种蛋白质，其中 5701 种是可定量的。与健康对照组相比，脓毒症大鼠组有 162 个上调和 103 个下调的差异表达蛋白（DEPs）。上调和下调的 DEPs 最显著地富集在补体和凝血级联反应以及代谢途径中。蛋白质-蛋白质相互作用（PPI）分析进一步表明，上调和下调的 DEPs 分别在 PPI 网络中聚类。一些高度连接的上调和下调的 DEPs 也分别富集到补体和凝血级联反应途径和代谢途径中。选定 DEPs 的平行反应监测（PRM）结果与 TMT 分析结果一致，支持蛋白质组学数据。
结论
本研究结果强调了补体和凝血级联反应以及代谢途径可能在宿主免疫反应中发挥重要作用。这些 DEPs 可能成为治疗脓毒性肝损伤的潜在临床治疗靶点。
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