Cherian M George, Kang Y James
Department of Pathology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Exp Biol Med (Maywood). 2006 Feb;231(2):138-44. doi: 10.1177/153537020623100203.
Hepatocytes in adults are in a nonproliferative state but they have high capacity to regenerate within few hours after an injury. After partial hepatectomy or chemical injury, hepatocytes undergo a synchronized multistep process consisting of priming/initiation, proliferation, and termination. These distinct steps are essential for restoring the structure and functions of liver. The mechanisms involved in each of these steps of regeneration are well documented from various laboratories and are described in several reviews. We briefly describe these steps and the involvement of various cytokines and growth factors for cell regeneration in this short review. Liver cell regeneration may also involve stem cell proliferation. The regenerating cells require large amounts of zinc within a short time, and this requirement is met by induction of a zinc and copper binding protein, metallothionein (MT), during the priming step, soon after an injury. There are several reports on the transfer of zinc from MT to various metalloenzymes and transcription factors. Genetically modified mouse models have been used to study the involvement of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in cell regeneration. The use of an MT-knockout mouse has enabled us to investigate the specific role of MT in liver regeneration after partial hepatectomy, chemical injury, and fibrosis. Several studies have suggested a defective liver regeneration after an injury in MT-knockout mice. There is cumulative evidence that indicates an essential role for MT in liver cell regeneration.
成体肝细胞处于非增殖状态，但在损伤后数小时内具有很高的再生能力。在部分肝切除或化学损伤后，肝细胞会经历一个同步的多步骤过程，包括启动/起始、增殖和终止。这些不同的步骤对于恢复肝脏的结构和功能至关重要。各个再生步骤所涉及的机制已在多个实验室得到充分记录，并在多篇综述中有所描述。在这篇简短的综述中，我们简要描述这些步骤以及各种细胞因子和生长因子在细胞再生中的作用。肝细胞再生也可能涉及干细胞增殖。再生细胞在短时间内需要大量锌，在损伤后不久的启动步骤中，通过诱导一种锌和铜结合蛋白——金属硫蛋白（MT）来满足这一需求。有几篇关于锌从MT转移到各种金属酶和转录因子的报道。转基因小鼠模型已被用于研究白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α在细胞再生中的作用。使用MT基因敲除小鼠使我们能够研究MT在部分肝切除、化学损伤和肝纤维化后肝脏再生中的具体作用。几项研究表明，MT基因敲除小鼠在损伤后肝脏再生存在缺陷。有累积证据表明MT在肝细胞再生中起重要作用。
