Autophagy regulates proliferation and biliary differentiation of hepatic oval cells via the MAPK/ERK signaling pathway

Chen,Dongdong; Wu,Xiaoxiao; Zheng,Jie; Dai,Ruijie; Mo,Zhichao; Munir,Fahad; Ni,Xiaolong; Shan,Yunfeng

doi:10.3892/mmr.2017.8157

Autophagy regulates proliferation and biliary differentiation of hepatic oval cells via the MAPK/ERK signaling pathway

Authors:
- Dongdong Chen
- Xiaoxiao Wu
- Jie Zheng
- Ruijie Dai
- Zhichao Mo
- Fahad Munir
- Xiaolong Ni
- Yunfeng Shan
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Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: November 27, 2017 https://doi.org/10.3892/mmr.2017.8157
Pages: 2565-2571

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Abstract

Hepatic oval cells (HOCs) are thought to possess self‑renewal ability and a bipotential capacity for differentiation, which allows them to differentiate into hepatocytes and cholangiocytes. Autophagy serves an important role in self‑renewal and differentiation of stem cells; however, how autophagy contributes to proliferation and differentiation of hepatic progenitor cells has yet to be elucidated. In the present study, autophagy was regulated by rapamycin (Rapa) and chloroquine (Chlo) administration. The results demonstrated that Chlo‑treated HOCs exhibited decreased autophagic activity alongside a decreased tendency to proliferate, as determined by Cell Counting Kit‑8. In addition, activation of autophagy by Rapa enhanced the biliary differentiation of HOCs. Furthermore, increased phosphorylated (p)‑extracellular signal‑regulated kinase (ERK)/p‑p38 expression was observed following the induction of autophagy, thus indicating that the mitogen‑activated protein kinase (MAPK)/ERK signaling pathway was activated by autophagy to exert effects on the stimulation of HOC proliferation and differentiation. In conclusion, the present study demonstrated that autophagy regulates proliferation and biliary differentiation of HOCs via the MAPK/ERK signaling pathway. These results suggest a role for autophagy in stimulating the proliferation and differentiation of HOCs.

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