INSERM U.1174, Université Paris Sud, bât. 443, 91405 Orsay, France; Université Paris Sud, bât. 443, 91405 Orsay, France.
ERL INSERM U 1057, Faculté de Médecine Pierre et Marie Curie, 27 rue Chaligny, 75571 Paris Cedex 12, France; UMR 7203, ENS, CNRS, UPMC, 27 rue Chaligny, 75571 Paris Cedex 12, France.
Mol Aspects Med. 2017 Aug;56:25-33. doi: 10.1016/j.mam.2017.03.002. Epub 2017 Mar 23.
Tissue repair is orchestrated by a finely tuned interplay between processes of regeneration, inflammation and cell protection, allowing organisms to restore their integrity after partial loss of cells or organs. An important, although largely unexplored feature is that after injury and during liver repair, liver functions have to be maintained to fulfill the peripheral demand. This is particularly critical for bile secretion, which has to be finely modulated in order to preserve liver parenchyma from bile-induced injury. However, mechanisms allowing the liver to maintain biliary homeostasis during repair after injury are not completely understood. Besides cytokines and growth factors, bile acids (BA) and their receptors constitute an insufficiently explored signaling network during liver regeneration and repair. BA signal through both nuclear (mainly Farnesoid X Receptor, FXR) and membrane (mainly G Protein-coupled BA Receptor 1, GPBAR-1 or TGR5) receptors which distributions are large in the organism, and which activation elicits a wide array of biological responses. While a number of studies have been dedicated to FXR signaling in liver repair processes, TGR5 remains poorly explored in this context. Because of the massive and potentially harmful BA overload that faces the remnant liver after partial ablation or destruction, both BA-induced adaptive and proliferative responses may stand in a central position to contribute to the regenerative response. Based on the available literature, both BA receptors may act in synergy during the regeneration process, in order to protect the remnant liver and maintain biliary homeostasis, otherwise potentially toxic BA overload would result in parenchymal insult and compromise optimal restoration of a functional liver mass.
组织修复是由再生、炎症和细胞保护过程的精细相互作用所协调的，使生物体在部分丧失细胞或器官后能够恢复其完整性。一个重要的、但在很大程度上尚未被探索的特征是，在受伤后和肝脏修复期间，肝脏功能必须得到维持，以满足外周的需求。这对于胆汁分泌尤其重要，为了防止肝实质因胆汁引起的损伤，必须精细地调节胆汁分泌。然而，在受伤后修复期间允许肝脏维持胆道内稳态的机制尚未完全被理解。除了细胞因子和生长因子外，胆汁酸（BA）及其受体在肝脏再生和修复过程中构成了一个未被充分探索的信号网络。BA 通过核（主要是法尼醇 X 受体，FXR）和膜（主要是 G 蛋白偶联 BA 受体 1，GPBAR-1 或 TGR5）受体发挥信号作用，这些受体在生物体中的分布广泛，其激活引发了广泛的生物学反应。虽然已经有许多研究致力于 FXR 信号在肝脏修复过程中的作用，但 TGR5 在这种情况下的研究仍然很少。由于部分切除或破坏后残余肝脏面临着大量且潜在有害的 BA 过载，BA 诱导的适应性和增殖反应可能处于中心位置，有助于再生反应。基于现有的文献，在再生过程中，两种 BA 受体可能协同作用，以保护残余肝脏并维持胆道内稳态，否则潜在的毒性 BA 过载会导致实质损伤，并损害功能肝脏质量的最佳恢复。
