Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice.
Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice.
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DOI：
10.1002/hep.28774
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发表时间：
2016-11
期刊：
影响因子：
13.5
通讯作者：
Nejak-Bowen, Kari Nichole
中科院分区：
文献类型：
--
作者：
Okabe, Hirohisa;Yang, Jing;Sylakowski, Kyle;Yovchev, Mladen;Miyagawa, Yoshitaka;Nagarajan, Shanmugam;Chikina, Maria;Thompson, Michael;Oertel, Michael;Baba, Hideo;Monga, Satdarshan P.;Nejak-Bowen, Kari Nichole
肝修复主要由常驻成熟上皮细胞的增殖指导。此外，如果主要损伤是胆管细胞，肝细胞可以转分化为胆管细胞，以帮助修复，反之亦然，如各种命运追踪研究所示。然而，重编程的分子基础仍然难以捉摸。使用两种模型的胆管损伤修复发生通过胆管细胞增殖和肝细胞转分化为胆管细胞，我们确定了一个重要的作用Wnt信号。首先，我们确定在胆管细胞中的特定Wnt蛋白的上调。接下来，使用Wntless和Wnt共受体LRP 5/6的条件性敲除、表达稳定β-连环蛋白的转基因小鼠和体外研究，我们显示了Wnt信号通过β-连环蛋白在肝细胞向胆汁转分化中的作用。最后，我们表明，特定的Wnt调节胆管细胞增殖，但在β-连环蛋白的非依赖性方式。结论：Wnt信号以β-catenin依赖和非依赖两种方式调节胆汁淤积性损伤后肝胆修复。
Hepatic repair is directed chiefly by the proliferation of resident mature epithelial cells. Further if predominant injury is to cholangiocytes, the hepatocytes can transdifferentiate to cholangiocytes to assist in the repair and vice versa as shown by various fate-tracing studies. However, the molecular bases of reprograming remain elusive. Using two models of biliary injury where repair occurs via cholangiocyte proliferation and hepatocyte transdifferentiation to cholangiocytes, we identify an important role of Wnt signaling. First we identify upregulation of specific Wnt proteins in the cholangiocytes. Next, using conditional knockouts of Wntless and Wnt co-receptors LRP5/6, transgenic mice expressing stable β-catenin, and in vitro studies, we show a role of Wnt signaling through β-catenin in hepatocyte to biliary transdifferentiation. Lastly, we show that specific Wnts regulate cholangiocyte proliferation but in a β-catenin-independent manner. Conclusion: Wnt signaling regulates hepatobiliary repair after cholestatic injury in both β-catenin dependent and independent manners.
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影响因子：
13.5
作者：
Nejak-Bowen, Kari N.;Thompson, Michael D.;Singh, Sucha;Bowen, William C., Jr.;Dar, Mohd Jamal;Khillan, Jaspal;Dai, Chunsun;Monga, Satdarshan P. S.
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作者：
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Trauner, Michael
影响因子：
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作者：
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