Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Int J Biochem Cell Biol. 2011 Feb;43(2):173-9. doi: 10.1016/j.biocel.2009.09.014. Epub 2009 Sep 27.
Loss of hepatic tissue triggers a regenerative response in the whole organ. Under typical normal conditions, all hepatic cells (epithelial: hepatocytes and biliary epithelial cells; non-epithelial: stellate cells, macrophages and endothelial cells) undergo one to three rounds of replication to establish the original number of cells and restore organ size. The review summarizes the literature of regenerative patterns in situations in which proliferation of either hepatocytes or biliary epithelial cells is inhibited. The evidence strongly suggests that under these circumstances, hepatocytes or biliary epithelial cells can function as facultative stem cells for each other and replenish the inhibited cellular compartment by a process of transdifferentiation, involving complex signaling pathways. These pathways are activated under experimental conditions in rodents and in fulminant hepatitis associated with liver failure in humans. Mechanistic analysis of these pathways has implications for liver biology and for potential therapeutic modalities in human liver disease.
肝脏组织的丧失会触发整个器官的再生反应。在典型的正常情况下，所有的肝细胞（上皮细胞：肝细胞和胆管上皮细胞；非上皮细胞：星状细胞、巨噬细胞和内皮细胞）都会进行一到三轮复制，以建立原始细胞数量并恢复器官大小。该综述总结了在抑制肝细胞或胆管上皮细胞增殖的情况下再生模式的文献。有证据强烈表明，在这些情况下，肝细胞或胆管上皮细胞可以作为彼此的多功能干细胞，并通过一种涉及复杂信号通路的转分化过程来补充受抑制的细胞区室。这些通路在实验条件下的啮齿动物和与人类肝功能衰竭相关的暴发性肝炎中被激活。对这些通路的机制分析对肝脏生物学和人类肝脏疾病的潜在治疗方法具有重要意义。
