Gut-Liver Axis: Liver Sinusoidal Endothelial Cells Function as the Hepatic Barrier in Colitis-Induced Liver Injury.
Gut-Liver Axis: Liver Sinusoidal Endothelial Cells Function as the Hepatic Barrier in Colitis-Induced Liver Injury.
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肠-肝轴：肝窦内皮细胞在结肠炎引起的肝损伤中充当肝屏障
DOI：
10.3389/fcell.2021.702890
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发表时间：
2021
影响因子：
5.5
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Wang Y;Zhang Y;Liu Y;Xu J;Liu Y
根据肠肝轴理论，肠漏可加重肝损伤。然而，临床研究表明，虽然在炎症性肠病（IBD）中常见肠黏膜损伤，但很少导致严重的肝损伤。我们假设在肠-肝轴上有一个肝屏障，它保护肝脏免受肠道源性侵袭因子的侵害。采用葡聚糖硫酸钠（DSS）诱导8种不同肝损伤模型大鼠结肠炎。采用扫描电镜和透射电镜观察肝窦内皮细胞（LSEC）损伤情况。注射抗大鼠多形核血清使中性粒细胞减少。同时，我们还诱导了两种肺炎模型来研究中性粒细胞募集和激活的机制。采用大鼠肝分离LSECs，观察其对中性粒细胞募集和活化的影响。在8个肝损伤模型中，DSS结肠炎对3个LSECs正常模型的肝损伤无影响。在LSEC破裂的其他5只模型中，结肠炎明显加重了肝损伤，肝中性粒细胞积累增加。当中性粒细胞减少时，结肠炎引起的肝损伤明显减轻。在肺炎、肝损伤和结肠炎模型中，CXCL1的表达水平与不同组织中中性粒细胞的募集相关，而DSS结肠炎和LSEC损伤协同促进了肝脏中CXCL1表达的增加。在结肠炎引起的肝损伤中，肝脏中的中性粒细胞被激活。损伤后的LSECs在结构和功能上均发生改变，在脂多糖（LPS）刺激下CXCL1和TNF-α的表达显著升高。肠道来源的LPS和lsec来源的TNF-α的结合导致中性粒细胞的激活，其特征是活性氧、促炎细胞因子的产生增强，以及中性粒细胞胞外陷阱的形成。LSECs在肠-肝轴中构成一个至关重要的屏障，保护肝脏免受结肠炎引起的损伤。当LSECs受损时，在LPS的刺激下，LSECs可转变为促炎模式。LSEC损伤和结肠炎源性LPS协同促进肝中性粒细胞的募集和激活。中性粒细胞在结肠炎引起的肝损伤中作为下游效应物发挥关键作用。
Based on the gut–liver axis theory, a leaky gut can aggravate liver injury. However, clinical studies suggest that although gut mucosa damage is commonly observed in inflammatory bowel disease (IBD), it seldom leads to severe liver injury. We hypothesize that there is a hepatic barrier in the gut–liver axis, which protects the liver against gut-derived invasive factors. Colitis was induced by dextran sulfate sodium (DSS) in eight different liver injury models in Sprague–Dawley rats. Liver sinusoidal endothelial cell (LSEC) injury was evaluated by a scanning and transmission electron microscope. Neutrophils were depleted by injection of anti-rat polymorphonuclear serum. Two pneumonia models were also induced to investigate the mechanism of neutrophil recruitment and activation. LSECs isolated from rat liver were used to investigate the effect on neutrophil recruitment and activation. Among eight liver injury models, DSS colitis had no effect on liver injury in three models with normal LSECs. In the other five models with LSEC rupture, liver injury was significantly exacerbated by colitis, and increased hepatic neutrophil accumulation was observed. When neutrophils were depleted, colitis-induced liver injury was significantly attenuated. In pneumonia, liver injury, and colitis models, the level of CXCL1 correlated with the recruitment of neutrophils in different tissues, while DSS colitis and LSEC injury synergistically contributed to increased CXCL1 expression in the liver. In colitis-induced liver injury, neutrophils were activated in the liver. Injured LSECs showed both structural and functional changes, with significantly increased expression of CXCL1 and TNF-α under the stimulation of lipopolysaccharide (LPS). The combination of gut-derived LPS and LSEC-derived TNF-α led to the activation of neutrophils, characterized by enhanced production of reactive oxygen species, pro-inflammatory cytokines, and the formation of neutrophil extracellular traps. LSECs constitute a vitally important barrier in the gut–liver axis, defending the liver against colitis-induced injury. When LSECs are damaged, they can turn into a pro-inflammatory pattern under the stimulation of LPS. LSEC injury and colitis-derived LPS synergistically contribute to the recruitment and activation of hepatic neutrophils. Neutrophils play a pivotal role as a downstream effector in colitis-induced liver injury.
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影响因子：
29.4
作者：
Feagan, Brian G.;McDonald, John W. D.;Greenberg, Gordon R.
通讯作者：
Greenberg, Gordon R.
影响因子：
7.4
作者：
Matsumoto M;Zhang J;Zhang X;Liu J;Jiang JX;Yamaguchi K;Taruno A;Katsuyama M;Iwata K;Ibi M;Cui W;Matsuno K;Marunaka Y;Itoh Y;Torok NJ;Yabe-Nishimura C
通讯作者：
Yabe-Nishimura C
影响因子：
2.1
作者：
Marshall, JC
通讯作者：
Marshall, JC
影响因子：
16.6
作者：
Kolaczkowska, Elzbieta;Jenne, Craig N.;Surewaard, Bas G. J.;Thanabalasuriar, Ajitha;Lee, Woo-Yong;Sanz, Maria-Jesus;Mowen, Kerri;Opdenakker, Ghislain;Kubes, Paul
通讯作者：
Kubes, Paul
损伤相关分子模式激活的中性粒细胞胞外陷阱加剧了无菌性炎症性肝损伤。
DOI：
10.1002/hep.27841
发表时间：
2015-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Huang H;Tohme S;Al-Khafaji AB;Tai S;Loughran P;Chen L;Wang S;Kim J;Billiar T;Wang Y;Tsung A
通讯作者：
Tsung A