Senescence suppressed proliferation of host hepatocytes is precondition for liver repopulation
Senescence suppressed proliferation of host hepatocytes is precondition for liver repopulation
复制标题
宿主肝细胞衰老抑制增殖是肝脏再生的先决条件
DOI：
10.1016/j.bbrc.2019.06.103
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发表时间：
2019-08-20
影响因子：
3.1
通讯作者：
Chen，Fei
中科院分区：
文献类型：
--
作者：
Chen，Jiajia;Yang，Tao;Chen，Fei
在富马酰乙酰乙酸水解酶缺陷（Fah−/−）小鼠中，移植肝细胞后可以很容易地获得大量的肝脏再生。了解Fah −/−小鼠肝脏完全再生的机制将有助于未来的临床应用。在这里，我们发现，内源性肝细胞在肝脏ofFah−/−小鼠进行衰老期间的酪氨酸血症症状。Fah −/−小鼠衰老肝细胞的增加为移植肝细胞提供了增殖优势。重要的是，衰老肝细胞上调细胞外基质酶的表达，导致细胞外基质成分的降解和细胞粘附和连接的减弱。肝脏结构疏松，为移植肝细胞的植入和扩增提供了空间。这些发现强调了在Fah −/−小鼠中完成肝脏再生的潜在机制。衰老后肝实质疏松是肝再生的预处理，这将是一个有前途的策略，以实现治疗性肝再生在临床设置。
In the fumarylacetoacetate hydrolase deficient (Fah−/−) mouse, massive liver repopulation can be easily obtained after transplanted hepatocytes. Understanding the mechanisms of complete liver repopulation inFah−/−mice will be useful for future clinical application. Here, we found that the endogenous hepatocytes in liver ofFah−/−mice undertook senescence during the time of tyrosinemia symptoms. Increase of senescent hepatocytes inFah−/−mice provided proliferative advantage to the transplanted hepatocytes. Importantly, senescent hepatocytes upregulated the expression of extracellular matrix enzyme, contributing to degradation of extracellular matrix components and weakness of cell adhesion and connection. The liver exhibiting a loose architecture provided the space for the engraftment and expansion of transplanted hepatocytes. These findings underscore the underlying mechanisms of completed liver repopulation inFah−/−mice. Senescence followed by loose hepatic parenchyma is a preconditioning for liver repopulation, which would be a promising strategy to achieve therapeutic liver repopulation in clinical settings.