Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China.
The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
Biomed Res Int. 2021 Apr 8;2021:6627506. doi: 10.1155/2021/6627506. eCollection 2021.
The molecular mechanisms regulating differentiation of hepatic progenitor cells (HPCs), which play pivotal roles in liver regeneration and development, remain obscure. Autophagy and Wnt signaling pathways regulate the development and differentiation of stem cells in various organs. However, the roles of autophagy and Wnt signaling pathways in hepatic differentiation of HPCs are not well understood. Here, we describe the effects of autophagy and Wnt signaling pathways during hepatic differentiation of HPCs. We used a well-established rat hepatic progenitor cell line called WB-F344, which was treated with differentiation medium to promote differentiation of WB-F344 cells along the hepatic phenotype. Firstly, autophagy was highly activated in HPCs and gradually decreased during hepatic differentiation of HPCs. Induction of autophagy by rapamycin or starvation suppressed hepatic differentiation of HPCs. Secondly, Wnt3a signaling pathway was downregulated, and Wnt5a signaling pathway was upregulated in hepatic differentiation of HPCs. At last, Wnt3a signaling pathway was enhanced, and Wnt5a signaling pathway was inhibited by activation of autophagy during hepatic differentiation of HPCs. In summary, these results demonstrate that autophagy regulates hepatic differentiation of hepatic progenitor cells through Wnt signaling pathway.
调控肝前体细胞（Hepatic progenitor cells，HPCs）分化的分子机制在肝脏再生和发育中起着关键作用，但目前尚不清楚。自噬和 Wnt 信号通路调节着各种器官中干细胞的发育和分化。然而，自噬和 Wnt 信号通路在 HPCs 的肝分化中的作用尚不清楚。在这里，我们描述了自噬和 Wnt 信号通路在 HPCs 的肝分化中的作用。我们使用了一种已建立的大鼠肝前体细胞系 WB-F344，用分化培养基处理该细胞系以促进 WB-F344 细胞沿着肝表型分化。首先，自噬在 HPCs 中高度激活，并在 HPCs 的肝分化过程中逐渐降低。雷帕霉素或饥饿诱导的自噬抑制 HPCs 的肝分化。其次，Wnt3a 信号通路在 HPCs 的肝分化过程中下调，而 Wnt5a 信号通路上调。最后，在 HPCs 的肝分化过程中，通过激活自噬增强了 Wnt3a 信号通路，抑制了 Wnt5a 信号通路。综上所述，这些结果表明自噬通过 Wnt 信号通路调节 HPCs 的肝分化。
