Clemens Melissa M, McGill Mitchell R, Apte Udayan
Interdisciplinary Biomedical Sciences Graduate Program, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Adv Pharmacol. 2019;85:241-262. doi: 10.1016/bs.apha.2019.03.001. Epub 2019 Mar 21.
Liver, the major metabolic organ in the body, is known for its remarkable capacity to regenerate. Whereas partial hepatectomy (PHx) is a popular model for the study of liver regeneration, the liver also regenerates after acute injury, but less is known about the mechanisms that drive it. Recent studies have shown that liver regeneration is critical for survival in acute liver failure (ALF), which is usually due to drug-induced liver injury (DILI). It is sometimes assumed that the signaling pathways involved are similar to those that regulate regeneration after PHx, but there are likely to be critical differences. A better understanding of regeneration mechanisms after DILI and hepatotoxicity in general could lead to development of new therapies for ALF patients and new biomarkers to predict patient outcome. Here, we summarize what is known about the mechanisms of liver regeneration and repair after hepatotoxicity. We also review the literature in the emerging field of liver regeneration biomarkers.
肝脏是人体主要的代谢器官，以其显著的再生能力而闻名。虽然部分肝切除术（PHx）是研究肝脏再生的常用模型，但肝脏在急性损伤后也会再生，不过驱动其再生的机制却鲜为人知。最近的研究表明，肝脏再生对于急性肝衰竭（ALF）患者的生存至关重要，急性肝衰竭通常由药物性肝损伤（DILI）引起。有时人们认为其中涉及的信号通路与调节PHx后再生的信号通路相似，但可能存在关键差异。更深入地了解DILI及一般肝毒性后的再生机制，可能会促成针对ALF患者的新疗法以及预测患者预后的新生物标志物的开发。在此，我们总结了关于肝毒性后肝脏再生和修复机制的已知信息。我们还综述了肝脏再生生物标志物这一新兴领域的文献。
