The role of paracrine signals during liver regeneration.
The role of paracrine signals during liver regeneration.
复制标题
旁分泌信号在肝再生过程中的作用。
DOI：
10.1002/hep.25911
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Greenbaum,Linda
中科院分区：
文献类型：
--
作者：
Stanger,BenZ;Greenbaum,Linda
在慢性损伤过程中，双能性肝祖细胞（HPCs）被激活再生胆管细胞和肝细胞。在人类病变肝脏和小鼠的导管反应模型中，我们发现Notch和Wnt信号通过与活化的肌成纤维细胞或巨噬细胞的相互作用直接指定HPCs。特别是，我们发现在胆道再生过程中，肌成纤维细胞表达Jagged 1（一种Notch配体）促进了HPCs中的Notch信号传导，从而促进了它们向胆管细胞的胆道规范。或者，在肝细胞再生过程中，巨噬细胞吞噬肝细胞碎片诱导Wnt3a表达。这导致附近HPCs中的典型Wnt信号，从而维持这些细胞内Numb（细胞命运决定因素）的表达，并促进其向肝细胞的特异性。在急性肝损伤过程中，这两种途径促进了成年实质的再生。
During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during acute liver injury is promoted.