Liver regeneration
Liver regeneration
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DOI：
10.1002/hep.20969
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发表时间：
2006-02-01
期刊：
影响因子：
13.5
通讯作者：
Riehle, KJ
中科院分区：
文献类型：
--
作者：
Fausto, N;Campbell, JS;Riehle, KJ
在部分肝切除术后的肝再生过程中，正常静止的肝细胞经历一轮或两轮复制，通过代偿性增生过程恢复肝脏质量。大量基因参与肝再生，但该过程所需的基本电路可分为三个网络：细胞因子，生长因子和代谢。每个网络内部都有很多冗余，它们之间存在复杂的交互。因此，单个基因的功能丧失很少导致肝再生的完全阻断。先天免疫系统在部分肝切除术后肝再生的启动中起着重要作用，并且已经鉴定了参与启动机制的新的细胞因子和受体。由这些试剂引发的肝细胞容易响应生长因子并进入细胞周期。据推测，对再生肝脏的肝细胞增加的代谢需求与肝细胞复制所需的机制有关，并且可以作为根据身体需求校准再生反应的传感器。与部分肝切除术后由现有肝细胞复制驱动的再生过程相反，急性肝功能衰竭后的肝脏再增殖取决于祖细胞的分化。这些细胞也存在于慢性肝病中，但它们在这些条件下对肝细胞产生的贡献尚不清楚。大多数关于肝再生的分子和细胞机制的新知识在概念上是重要的，并且与临床问题直接相关。
During liver regeneration after partial hepatectomy, normally quiescent hepatocytes undergo one or two rounds of replication to restore the liver mass by a process of compensatory hyperplasia. A large number of genes are involved in liver regeneration, but the essential circuitry required for the process may be categorized into three networks: cytokine, growth factor and metabolic. There is much redundancy within each network, and intricate interactions exist between them. Thus, loss of function from a single gene rarely leads to complete blockage of liver regeneration. The innate immune system plays an important role in the initiation of liver regeneration after partial hepatectomy, and new cytokines and receptors that participate in initiation mechanisms have been identified. Hepatocytes primed by these agents readily respond to growth factors and enter the cell cycle. Presumably, the increased metabolic demands placed on hepatocytes of the regenerating liver are linked to the machinery needed for hepatocyte replication, and may function as a sensor that calibrates the regenerative response according to body demands. In contrast to the regenerative process after partial hepatectomy, which is driven by the replication of existing hepatocytes, liver repopulation after acute liver failure depends on the differentiation of progenitor cells. Such cells are also present in chronic liver diseases, but their contribution to the production of hepatocytes in those conditions is unknown. Most of the new knowledge about the molecular and cellular mechanisms of liver regeneration is both conceptually important and directly relevant to clinical problems.