胆汁酸受体TGR5对肝脏的保护作用。,Liver International

当前位置： X-MOL 学术 › Liver Int. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

胆汁酸受体TGR5对肝脏的保护作用。
Liver International ( IF 6.0 ) Pub Date : 2020-03-30 , DOI: 10.1111/liv.14427
Grégory Merlen ₁ , Valeska Bidault-Jourdainne ₁ , Nicolas Kahale ₁ , Mathilde Glenisson ₁ , José Ursic-Bedoya ₁ , Isabelle Doignon ₁ , Isabelle Garcin ₁ , Lydie Humbert ₂ , Dominique Rainteau ₂ , Thierry Tordjmann ₁

Affiliation

在损伤后的肝修复过程中，必须严格调节胆汁的分泌，以保护肝实质免于胆汁酸（BA）诱导的损伤。损伤后修复过程中允许肝脏维持胆道稳态的机制尚不完全清楚。胆汁酸（BA）及其受体除了在脂质消化中的历史作用外，还构成了对肝脏修复有多重影响的信号网络，既刺激了再生又保护了肝脏免于BA超负荷。BA信号通过核受体（主要是Farnesoid X受体，FXR）和膜（主要是G蛋白偶联BA受体1，GPBAR-1或TGR5）受体引起广泛的生物学反应。尽管针对FXR信号的肝脏保护作用进行了大量研究，但在这种情况下，关于TGR5的研究还很少。由于肝脏在部分消融或破坏后必须面对大量且可能有害的BA超负荷，因此BA诱导的保护性反应至关重要，有助于剩余的肝修复能力。根据现有文献，TGR5 BA受体主要通过控制炎症，胆道上皮屏障通透性，BA池疏水性和正弦血流来保护残余肝并维持胆道稳态。小鼠肝损伤实验模型表明，在缺乏TGR5的情况下，过度炎症，胆道上皮渗漏和疏水性BA超负荷会导致实质损害，并损害功能性肝块的最佳恢复。因此，打开了针对TGR5的转化视角，目的是在损伤和BA超负荷的情况下保护肝脏。

"点击查看英文标题和摘要"

Hepatoprotective impact of the bile acid receptor TGR5.

During liver repair after injury, bile secretion has to be tightly modulated in order to preserve liver parenchyma from bile acid (BA)-induced injury. The mechanisms allowing the liver to maintain biliary homeostasis during repair after injury are not completely understood. Besides their historical role in lipid digestion, bile acids (BA) and their receptors constitute a signalling network with multiple impacts on liver repair, both stimulating regeneration and protecting the liver from BA overload. BA signal through nuclear (mainly Farnesoid X Receptor, FXR) and membrane (mainly G Protein-coupled BA Receptor 1, GPBAR-1 or TGR5) receptors to elicit a wide array of biological responses. While a great number of studies have been dedicated to the hepato-protective impact of FXR signalling, TGR5 is by far less explored in this context. Because the liver has to face massive and potentially harmful BA overload after partial ablation or destruction, BA-induced protective responses crucially contribute to spare liver repair capacities. Based on the available literature, the TGR5 BA receptor protects the remnant liver and maintains biliary homeostasis, mainly through the control of inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity and sinusoidal blood flow. Mouse experimental models of liver injury reveal that in the lack of TGR5, excessive inflammation, leaky biliary epithelium and hydrophobic BA overload result in parenchymal insult and compromise optimal restoration of a functional liver mass. Translational perspectives are thus opened to target TGR5 with the aim of protecting the liver in the context of injury and BA overload.

更新日期：2020-03-30

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南