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Updated: Aug 7, 2025
Immunolabelling Myofiber Degeneration in Muscle Biopsies
Published on: December 5, 2019
TWEAK and Fn14 are overexpressed in immune-mediated necrotizing myopathy: implications for muscle damage and repair
Mengge Yang1, Huizhen Ge1, Suqiong Ji1
1Department of Neurology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Objectives:
TNF-like weak inducer of apoptosis (TWEAK) and its sole receptor fibroblast growth factor-inducible 14 (Fn14) are involved in various inflammatory conditions. This study was performed to investigate the potential role of TWEAK/Fn14 in immune-mediated necrotizing myopathy (IMNM).
Methods:
Muscle biopsies from patients with IMNM (n = 37) and controls (n = 11) were collected. Human muscle cells were treated with TWEAK in vitro. Muscle biopsies and cultured muscle cells were analysed by immunostaining and quantitative PCR. Serum levels of TWEAK and Fn14 were detected by ELISA.
Results:
TWEAK and Fn14 were overexpressed in IMNM muscle biopsies. The percentage of Fn14-positive myofibers correlated with disease severity, myonecrosis, regeneration and inflammation infiltrates. Fn14-positive myofibers tended to be surrounded or invaded by CD68+ macrophages. TWEAK treatment had a harmful effect on cultured muscle cells by inducing the production of multiple chemokines and pro-inflammatory cytokines. Serum Fn14 levels were increased in patients with IMNM and correlated with muscle weakness.
Conclusions:
TWEAK/Fn14 signalling was activated in IMNM, most likely aggravating muscle damage via amplifying inflammatory response and macrophages chemotaxis. Fn14 seems to be a biomarker for assessing disease severity in IMNM. In addition, Fn14 may also contribute to muscle injury repair.
Insights
The TWEAK/Fn14 pathway is active in immune-mediated necrotizing myopathy (IMNM), worsening muscle damage and inflammation. Fibroblast growth factor-inducible 14 (Fn14) may serve as a biomarker for IMNM severity.
Area of Science:
- Immunology
- Pathology
- Molecular Biology
Background:
- TNF-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are implicated in inflammatory diseases.
- Their specific role in immune-mediated necrotizing myopathy (IMNM) remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of the TWEAK/Fn14 signaling pathway in the pathogenesis of IMNM.
- To assess the potential of TWEAK/Fn14 as biomarkers for IMNM severity and progression.
Main Methods:
- Analysis of muscle biopsies from IMNM patients and controls using immunostaining and quantitative PCR.
- In vitro studies involving TWEAK treatment of human muscle cells.
- Quantification of serum TWEAK and Fn14 levels via ELISA.
Main Results:
- Overexpression of TWEAK and Fn14 was observed in IMNM muscle tissue.
- Higher Fn14 expression in myofibers correlated with increased disease severity, myonecrosis, and inflammation.
- TWEAK exposure induced pro-inflammatory cytokine and chemokine production in muscle cells.
- Elevated serum Fn14 levels in IMNM patients correlated with muscle weakness.
Conclusions:
- TWEAK/Fn14 signaling is activated in IMNM, likely exacerbating muscle damage by enhancing inflammation and macrophage recruitment.
- Fn14 shows potential as a biomarker for assessing IMNM disease severity.
- The pathway may also play a role in muscle injury repair mechanisms.
