Human liver tissue transcriptomics revealed immunometabolic disturbances and related biomarkers in hepatitis B virus-related acute-on-chronic liver failure.
Human liver tissue transcriptomics revealed immunometabolic disturbances and related biomarkers in hepatitis B virus-related acute-on-chronic liver failure.
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DOI：
10.3389/fmicb.2022.1080484
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发表时间：
2022
影响因子：
5.2
通讯作者：
Xie, Chan
中科院分区：
文献类型：
--
作者：
Yang, Luo;Zhen, Limin;Li, Zhihui;Zhu, Shu;Xu, Wenxiong;Luo, Qiumin;Peng, Liang;Xie, Chan
急性慢性肝衰竭（ACLF）是世界范围内肝脏相关死亡的主要原因，但其主要病理特征尚未完全确定。本研究旨在通过人肝组织转录组测序揭示乙型肝炎病毒相关ACLF （HBV-ACLF）的分子基础。收集来自不同阶段hbv相关疾病患者的18个人肝组织进行RNA测序，并使用ACLF患者和小鼠模型的肝组织进行后续验证。具体而言，与慢性乙型肝炎（CHB）患者和正常对照（nc）相比，ACLF患者中鉴定出6853个差异表达基因（deg）和5038个差异表达转录物。通过KEGG通路富集分析功能调查显示，ACLF阶段存在明显的免疫和代谢失调。我们发现与免疫代谢紊乱相关的关键基因FGF19、ADCY8和KRT17在ACLF的进展过程中显著上调。这三个关键基因在人类和小鼠样本中得到验证，表明它们在ACLF中的预后和治疗潜力。综上所述，我们的工作揭示了免疫代谢紊乱参与了HBV-ACLF的发病机制，并表明FGF19、ADCY8和KRT17可能是hbv相关ACLF的敏感生物标志物。
Acute-on-chronic liver failure (ACLF) is a major cause of liver-related death worldwide, but its key pathological features remain incompletely defined. This study aimed to reveal the molecular basis of hepatitis B virus-related ACLF (HBV-ACLF) by transcriptome sequencing of human liver tissue. A total of 18 human liver tissues from patients with different stages of HBV-related disease were collected for RNA sequencing, and liver tissues from patients and mouse models with ACLF were used for subsequent validation. Specifically, 6,853 differentially expressed genes (DEGs) and 5,038 differentially expressed transcripts were identified in patients with ACLF compared to patients with chronic hepatitis B (CHB) and normal controls (NCs). Investigation of functional by KEGG pathway enrichment analysis revealed prominent immune and metabolic dysregulation at the ACLF stage. We found that the key genes FGF19, ADCY8 and KRT17, which are related to immunometabolic disturbances, were significantly upregulated in the progression of ACLF. The three key genes were validated in human and mouse samples, indicating their prognostic and therapeutic potential in ACLF. In summary, our work reveals that immunometabolic disorder is involved in HBV-ACLF pathogenesis and indicates that FGF19, ADCY8 and KRT17 may be sensitive biomarkers for HBV-related ACLF.
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影响因子：
3.6
作者：
通讯作者：
--
转录组学揭示大鼠慢加急性肝衰竭的免疫代谢紊乱
影响因子：
4.4
作者：
Hassan HM;Cai Q;Liang X;Xin J;Ren K;Jiang J;Shi D;Lu Y;Li T;Shang Y;He L;Chen X;Sun S;Li P;Guo B;Chen J;Yang H;Hu W;Chen X;Li J
通讯作者：
Li J
DOI：
10.1093/toxsci/kfu160
发表时间：
2014-11
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
--
作者：
Kyriakides M;Hardwick RN;Jin Z;Goedken MJ;Holmes E;Cherrington NJ;Coen M
通讯作者：
Coen M
影响因子：
7.7
作者：
Bozadjieva N;Heppner KM;Seeley RJ
通讯作者：
Seeley RJ
影响因子：
8.2
作者：
Roger, B.;Papin, J.;Lang, J.
通讯作者：
Lang, J.