Int J Biol Sci 2021; 17(3):861-868. doi:10.7150/ijbs.56091 This issue

Research Paper

PTEN-mediated AKT/β-catenin signaling enhances the proliferation and expansion of Lgr5+ hepatocytes

Jimin Han1*, Kaijun Lin1*, Xuezheng Zhang1*, Lingchen Yan1*, Jianjun Liu2, Jia Liu1✉

1. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China.
2. Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, 518054, Shenzhen, China.
* These authors are the first authors of this paper.

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Citation:
Han J, Lin K, Zhang X, Yan L, Liu J, Liu J. PTEN-mediated AKT/β-catenin signaling enhances the proliferation and expansion of Lgr5+ hepatocytes. Int J Biol Sci 2021; 17(3):861-868. doi:10.7150/ijbs.56091. Available from https://www.ijbs.com/v17p0861.htm

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Abstract

Graphic abstract

Rationale: Compelling evidence suggests that Lgr5+ hepatocytes repair liver damage by promoting the regeneration of hepatocytes and ductal cells in the case of liver injury. The PTEN-mediated AKT/β-catenin signaling plays a key role in the regulation of innate immune regulation in the liver. However, the signaling pathways that control Lgr5+ hepatocyte proliferation in the liver remain unclear.

Methods: In order to assess the involvement of PTEN-mediated AKT/β-catenin signaling in the expansion of Lgr5+ hepatocytes upon liver injuries, the Lgr5-CreER; Rosa-mTmG lineage tracing system was used to target Lgr5+ hepatocytes.

Results: The tracing of Lgr5+ hepatocytes showed that PTEN deletion and β-catenin activation significantly promoted the proliferation of Lgr5+ hepatocytes. In converse, the simultaneous inhibition of PTEN and β-catenin limited Lgr5+ hepatocyte proliferation in the liver. Our findings provide an insight into understanding how PTEN-mediated AKT/β-catenin signaling regulates the proliferation of Lgr5+ hepatocytes.

Conclusion: The outcomes can improve the application potential of Lgr5+ hepatocytes in the treatment of liver injury diseases and provide a new treatment option for liver cancer.

Keywords: AKT/β-catenin, Lgr5, hepatocyte, proliferation, liver regeneration.