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

: 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 sig...

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Bibliographic Details
Published in:International journal of biological sciences 2021-01, Vol.17 (3), p.861-868
Main Authors: Han, Jimin, Lin, Kaijun, Zhang, Xuezheng, Yan, Lingchen, Chen, Yu, Chen, Haiyan, Liu, Jianjun, Liu, Jia, Wu, Yaojiong
Format: Article
Language:English
Subjects:
AKT protein
Animals
Artificial chromosomes
beta Catenin - metabolism
Bile ducts
Cell division
Colon
Efficiency
Hepatocytes
Hepatocytes - physiology
Homeostasis
Immunoregulation
Injuries
Ischemia
Kinases
Liver
Liver cancer
Liver diseases
Liver Regeneration
Mice, Transgenic
Proto-Oncogene Proteins c-akt - metabolism
PTEN Phosphohydrolase - physiology
PTEN protein
Receptors, G-Protein-Coupled - physiology
Regeneration
Research Paper
Signaling
Small intestine
Stem cells
Tracing
β-Catenin
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Summary:: 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. : 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. 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. 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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.56091