The impact and mechanism of TET3 overexpression on the progression of hepatic fibrosis

Epigenomics. 2023 May;15(10):577-591. doi: 10.2217/epi-2023-0146. Epub 2023 Jul 18.

Abstract

Aims: To investigate whether TET3 regulates hepatic stellate cell apoptosis and understand the role of demethylation in hepatic fibrosis (HF). Methods: LX-2T cells were infected with TET3 lentivirus. After TET3 adenovirus infection, the degree of HF in each group was analyzed. Chromatin immunoprecipitation was used to verify the targeting relationship between TET3 and CBP, and finally the expression of various proteins was detected. Results: TET3 overexpression activated the CBP/FOXO1-BIM pathway, increased the expression of apoptotic proteins and accelerated the apoptosis of activated LX-2 cells. The degree of HF was improved in the TET3 upregulation group. Conclusion: TET3 can activate the CBP/FOXO1-BIM pathway to accelerate the apoptosis of activated hepatic stellate cells and ultimately alleviate HF.

Keywords: CBP/FOXO1–BIM pathway; apoptosis; demethylase TET3; hepatic fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Dioxygenases* / metabolism
  • Humans
  • Liver Cirrhosis* / genetics
  • Liver Cirrhosis* / metabolism
  • Up-Regulation

Substances

  • TET3 protein, human
  • Dioxygenases