Liver regeneration
Liver regeneration
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DOI：
10.1016/s0168-8278(00)80412-2
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发表时间：
2000-01-01
影响因子：
25.7
通讯作者：
Fausto, N
中科院分区：
文献类型：
--
作者：
Fausto, N
肝脏可以精确地调节其生长和质量。肝叶的手术切除或由病毒或化学损伤引起的肝细胞损失触发肝细胞复制，而增大的肝脏质量通过凋亡得到纠正。肝细胞具有很大的复制能力，并且能够重新填充肝脏。然而，当肝细胞复制被阻断或延迟时，“干细胞样”细胞增殖。已经在部分肝切除或化学损伤的动物中进行了调节肝脏生长的机制的详细研究。使用适当的转基因和基因敲除小鼠模型进行这项工作已经取得了实质性进展。再生肝脏中的基因表达可以分为几个阶段，从大量立即早期基因的表达开始。肝细胞需要在体外对生长因子HGF（肝细胞生长因子）、TGF α（转化生长因子α）和EGF（表皮生长因子）完全应答之前进行预处理。引发需要细胞因子TNF和IL-6以及防止细胞毒性的其他试剂。活性氧和谷胱甘肽含量可以决定TNF对肝细胞的作用是增殖还是凋亡。至少有四种转录因子NF κ B、STAT 3（它们被TNF强烈诱导）、AP-1和C/EBP β在肝再生的启动中起主要作用。此外，肝细胞外基质的广泛重塑发生在部分肝切除术后不久，通过细胞周期的进展超过起始阶段需要生长因子。细胞周期蛋白D1的表达可能建立了复制成为生长因子独立和自主的阶段。关于肝再生机制的知识现在可以应用于纠正由肝脏生长不足引起的临床问题。
The liver can precisely regulate its growth and mass. Surgical resection of hepatic lobes or hepatocyte loss caused by viral or chemical injury triggers hepatocyte replication while enlarged liver mass is corrected by apoptosis, Hepatocytes have a great replicative capacity and are capable of repopulating the liver. However, "stem-like" cells proliferate when hepatocyte replication is blocked or delayed. Detailed studies of the mechanisms that regulate liver growth have been done in animals subjected to partial hepatectomy or chemical injury Substantial progress has been achieved using appropriate transgenic and knockout mouse models for this work. Gene expression in the regenerating liver can be divided into several phases, starting with expression of a large number of immediate early genes. Hepatocytes need to be primed before they can fully respond to the growth factors HGF (Hepatocyte Growth Factor), TGF alpha (Transforming Growth Factor Alpha), and EGF (Epidermal Growth Factor) in vitro. Priming requires the cytokines TNF and IL-6 in addition to other agents that prevent cytotoxicity. Reactive Oxygen Species and glutathione content can determine whether the TNF effect on hepatocytes is proliferative or apoptotic, At least four transcription factors, NF kappa B, STAT3 (which are strongly induced by TNF), AP-1 and C/EBP beta play major roles in the initiation of liver regeneration. In addition, extensive remodeling of the hepatic extracellular matrix occurs shortly after partial hepatectomy, Progression through the cell cycle beyond the initiation phase requires growth factors. The expression of Cyclin D1 probably establishes the stage at which replication becomes growth factor-independent and autonomous. Knowledge about the mechanisms of liver regeneration can now be applied to correct clinical problems caused by deficient liver growth.