Related Experiment Video

Updated: Sep 17, 2025

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
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IFNα/JAK/STAT1 Axis-Induced FBXO4 Modulates Muscle Cell Differentiation via β-Catenin Degradation in Dermatomyositis

Liguo Yin1,2, Hanbo Yang3, Min Fu1,2

  • 1Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.

Journal of Inflammation Research
|July 2, 2025
PubMed
Abstract

Insights

The ubiquitin E3 ligase FBXO4 is upregulated in dermatomyositis (DM), inhibiting muscle cell differentiation and promoting apoptosis. Targeting FBXO4 may offer a novel therapeutic strategy for DM patients.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Dermatomyositis (DM) is a chronic inflammatory myopathy with unclear pathogenesis.
  • The role of ubiquitin E3 ligases in DM pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the biological roles of ubiquitin E3 ligases in DM.
  • To identify specific ubiquitin E3 ligases involved in DM muscle pathology.

Main Methods:

  • Differential gene expression analysis using Deseq2 on public DM datasets.
  • Quantitative real-time PCR and Western blot for mRNA and protein validation.
  • Co-immunoprecipitation and dual-luciferase reporter assays for protein interactions and regulatory mechanisms.

Main Results:

  • FBXO4, a ubiquitin E3 ligase, was significantly upregulated in DM muscle tissues.
  • FBXO4 knockout in muscle cells promoted differentiation and inhibited cell cycle pathways.
  • FBXO4 ubiquitinates and degrades β-catenin, inhibiting Wnt/β-catenin signaling and muscle differentiation, and may promote apoptosis by degrading MCL1.
  • FBXO4 expression is regulated by the IFNα/JAK/STAT1 pathway and is a direct target of STAT1.

Conclusions:

  • The IFNα/JAK/STAT1 pathway upregulates FBXO4 in DM, contributing to muscle atrophy by inhibiting differentiation and promoting apoptosis.
  • Targeting FBXO4 presents a potential novel therapeutic strategy for dermatomyositis.
Keywords:
FBXO4IFNα/JAK/STAT1 axisWnt/β-catenin signalingdermatomyositismuscle cell differentiation

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