The Impact and Mechanism of TET3 Overexpression on the Progression of Hepatic Fibrosis

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::

• apoptosis
• CBP/FOXO1–BIM pathway
• demethylase TET3
• hepatic fibrosis

Author Contributions

R Liu: conceptualization, methodology, writing (original draft). R Liu, L Feng: formal analysis, resources, investigation. R Liu, S Tang: formal analysis, visualization, data curation. Q Yang: validation, supervision, writing (review and editing).

Acknowledgments

The authors would like to express their gratitude to EditSprings (www.editsprings.cn) for the expert linguistic services provided.

Financial & competing interests disclosure

This work was funded by the National Natural Sciences Foundation of China (no. 81560105). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal experiments complied with the ARRIVE guidelines and were approved by the Ethics Committee of the Guizhou Medical University.

Additional information

Funding

This work was funded by the National Natural Sciences Foundation of China (no. 81560105). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.