Li Guodong, L Guo Grace
Department of General Surgery, the Fourth Hospital of Harbin Medical University, Harbin 150001, China ; Division of Biobank Research, Department of General Surgery, the Fourth Hospital of Harbin Medical University, Harbin 150001, China.
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA.
Acta Pharm Sin B. 2015 Mar;5(2):93-8. doi: 10.1016/j.apsb.2015.01.005. Epub 2015 Feb 20.
The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy (PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids (BAs) are ligands of farnesoid X receptor (FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potential use of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.
肝脏在再生潜能方面独具特色,在经历缺血和切除损伤后,它能够恢复损失的质量和功能。过去,人们利用啮齿动物的部分肝切除术(PH)模型,对肝脏再生的潜在分子机制进行了广泛研究,其中通过切除两个叶来实施2/3 PH。肝脏再生的整个过程十分复杂,是一个由相互关联的网络相互作用精心编排的过程,目前仍完全难以捉摸。胆汁酸(BAs)是法尼醇X受体(FXR)的配体,FXR是一种配体激活转录因子的核受体。研究表明,FXR高度参与肝脏再生。在肝脏再生过程中,BAs和FXR不仅相互作用,还各自调节各种下游靶点。此外,最近的研究结果表明,组织特异性FXR对肝脏再生也有显著贡献。这些新发现表明,FXR的作用远比调节胆汁酸、胆固醇、脂质和葡萄糖代谢更为广泛。因此,这些研究突出了FXR作为一个重要的药物靶点,有望在临床上使用FXR配体来调节肝脏再生。本综述重点关注BAs和FXR在肝脏再生中的作用以及目前有助于肝脏再生的潜在分子机制。