Rudnick David A, Davidson Nicholas O
Department of Pediatrics, Washington University School of Medicine, P.O. Box 8208, St. Louis, MO 63110, USA.
Int J Hepatol. 2012;2012:549241. doi: 10.1155/2012/549241. Epub 2012 Jan 26.
The regenerative capacity of the liver is well known, and the mechanisms that regulate this process have been extensively studied using experimental model systems including surgical resection and hepatotoxin exposure. The response to primary mitogens has also been used to investigate the regulation of hepatocellular proliferation. Such analyses have identified many specific cytokines and growth factors, intracellular signaling events, and transcription factors that are regulated during and necessary for normal liver regeneration. Nevertheless, the nature and identities of the most proximal events that initiate hepatic regeneration as well as those distal signals that terminate this process remain unknown. Here, we review the data implicating acute alterations in lipid metabolism as important determinants of experimental liver regeneration and propose a novel metabolic model of regeneration based on these data. We also discuss the association between chronic hepatic steatosis and impaired regeneration in animal models and humans and consider important areas for future research.
肝脏的再生能力是众所周知的，并且利用包括手术切除和肝毒素暴露在内的实验模型系统，对调节这一过程的机制进行了广泛研究。对原发性有丝分裂原的反应也已被用于研究肝细胞增殖的调控。此类分析已确定了许多在正常肝再生过程中受到调控且为其正常进行所必需的特定细胞因子、生长因子、细胞内信号事件和转录因子。然而，启动肝再生的最近端事件的性质和特征以及终止这一过程的远端信号仍然未知。在此，我们回顾了表明脂质代谢急性改变是实验性肝再生重要决定因素的数据，并基于这些数据提出了一种新的再生代谢模型。我们还讨论了动物模型和人类中慢性肝脂肪变性与再生受损之间的关联，并考虑了未来研究的重要领域。
