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Updated: Jul 13, 2025

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Tripartite motif containing 26 prevents steatohepatitis progression by suppressing C/EBPδ signalling activation

Minxuan Xu1,2, Jun Tan3, Xin Liu4

  • 1Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, 400067, Chongqing, P. R. China. minxuanxu@foxmail.com.

Nature Communications
|October 11, 2023
PubMed

Insights

Tripartite motif containing 26 (TRIM26) suppresses nonalcoholic steatohepatitis (NASH) by degrading CCAAT/enhancer binding protein delta (C/EBPδ). TRIM26 protects against NASH progression, offering a potential therapeutic target.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Biochemistry

Background:

  • Nonalcoholic steatohepatitis (NASH) pathogenesis is complex, hindering therapeutic development.
  • Existing preclinical drugs for NASH often fail due to intricate disease mechanisms.

Purpose of the Study:

  • To identify key regulators of NASH pathogenesis.
  • To investigate the role of Tripartite motif containing 26 (TRIM26) in liver metabolic homeostasis and NASH progression.

Main Methods:

  • Investigated TRIM26 as a suppressor of CCAAT/enhancer binding protein delta (C/EBPδ).
  • Confirmed TRIM26 interaction with C/EBPδ and its role in ubiquitin-proteasome degradation.
  • Utilized hepatocyte-specific Trim26 loss and overexpression models in rodent and rabbit NASH models.

Main Results:

  • TRIM26 directly interacts with C/EBPδ, catalyzing its ubiquitination and degradation in hepatocytes.
  • Loss of hepatocyte TRIM26 leads to metabolic dysfunction, inflammation, fibrosis, and accelerated NASH.
  • Overexpression of TRIM26 ameliorates NASH phenotypes in animal models.

Conclusions:

  • TRIM26 is a critical endogenous suppressor of C/EBPδ and NASH development.
  • TRIM26 regulates liver metabolic homeostasis and mitigates NASH progression.
  • TRIM26 represents a potential therapeutic target for NASH treatment.

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