Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.
Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.
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DOI：
10.3390/jcm11102910
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发表时间：
2022-05-20
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
慢性加急性肝衰竭（ACLF）是一种急性失代偿性肝硬化综合征，具有较高的短期死亡率。关于淋巴系统和ACLF之间的关系知之甚少。我们使用人类肝脏样本，借助单细胞RNA测序（scRNA-seq）技术，探索肝淋巴管（LV）和淋巴管内皮细胞（LyEC）在ACLF中的作用。在这里，ACLF表现出比肝硬化更严重的肝损伤和炎症，如丙氨酸/天冬氨酸转氨酶和总胆红素的血浆水平显着增加所示。与肝硬化组相比，ACLF组肝内LV数量明显减少。ScRNA-seq显示ACLF病例的肝脏中有许多单核/巨噬细胞浸润。同时，scRNA-seq揭示了一组凋亡和功能障碍的LyEC，这是从浸润的单核细胞/巨噬细胞释放的分泌型磷蛋白1（SPP 1）的结果。在体外实验中，SPP 1可显著增加LyECs死亡的比例，并以剂量和时间依赖的方式损害LyECs的管状形成能力。总之，ACLF与LV和LyEC功能障碍较少相关，至少部分由浸润单核细胞/巨噬细胞释放的SPP 1介导。肝LV和LyEC可以成为ACLF的新治疗策略。
Acute-on-chronic liver failure (ACLF) is an acutely decompensated cirrhosis syndrome with high short-term mortality. Very little is known about the relationship between the lymphatic system and ACLF. We explored the role of hepatic lymphatic vessels (LVs) and lymphatic endothelial cells (LyECs) in ACLF using human liver samples with the help of single-cell RNA-sequencing (scRNA-seq) technology. Here, ACLF exhibited more severe liver injury and inflammation than cirrhosis, as indicated by significant increases in plasma levels of alanine/aspartate aminotransferases and total bilirubin. Compared with cirrhosis cases, the number of intrahepatic LVs was decreased significantly in ACLF patients. ScRNA-seq revealed that many monocyte/macrophages infiltrated into the liver of ACLF cases. Meanwhile, scRNA-seq revealed a group of apoptotic and dysfunctional LyECs, which were the result of secreted phosphoprotein 1 (SPP1) released from infiltrating monocyte/macrophages. In vitro, SPP1 increased the proportion of dead LyECs significantly and impaired the ability of tube formation of LyECs in a dose- and time-dependent manner. In conclusion, ACLF is associated with less LV and LyEC dysfunction, at least in part mediated by SPP1 released from infiltrating monocyte/macrophages. Hepatic LVs and LyECs can be a novel therapeutic strategy for ACLF.
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影响因子：
30.5
作者：
Arazi, Arnon;Rao, Deepak A.;Goldman, Daniel H.
通讯作者：
Goldman, Daniel H.
影响因子：
6
作者：
Casulleras M;Zhang IW;López-Vicario C;Clària J
通讯作者：
Clària J
DOI：
10.1016/j.jcmgh.2020.09.007
发表时间：
2021
影响因子：
7.2
作者：
Burchill MA;Finlon JM;Goldberg AR;Gillen AE;Dahms PA;McMahan RH;Tye A;Winter AB;Reisz JA;Bohrnsen E;Schafer JB;D'Alessandro A;Orlicky DJ;Kriss MS;Rosen HR;McCullough RL;Jirón Tamburini BA
通讯作者：
Jirón Tamburini BA
影响因子：
4
作者：
Honarpisheh M;Desai J;Marschner JA;Weidenbusch M;Lech M;Vielhauer V;Anders HJ;Mulay SR
通讯作者：
Mulay SR
影响因子：
1.2
作者：
Kegel, Victoria;Deharde, Daniela;Damm, Georg
通讯作者：
Damm, Georg