Mitochondrial morphology and MAVS-IFN1 signaling pathway in muscles of anti-MDA5 dermatomyositis.

Abstract

OBJECTIVE:

This study aimed to investigate mitochondrial changes and the mitochondrial antiviral-signaling protein (MAVS)-type I interferon (IFN1) signaling pathway in the muscles of anti-melanoma differentiation gene 5(MDA5) dermatomyositis (DM) patients.

METHODS:

Eleven anti-MDA5 DM and ten antibody-negative DM patients were included. Muscle biopsies were performed in all patients. Muscle pathology and mitochondrial morphology in particular were compared between two groups. The expression of MDA5, MAVS, interferon (IFN) regulatory factor 7, and IFN-stimulated gene 15, which are components of the MAVS-IFN1 signaling pathway, was measured in muscle specimen. The correlation between MAVS expression in muscles and disease phenotypes and muscle pathology were analyzed.

RESULTS:

Anti-MDA5 DM showed a significantly lower incidence of the characteristic DM pathology (P < 0.05) than antibody-negative DM, including perifascicular fiber atrophy, inflammation, and vasculopathy. Mitochondrial abnormalities in anti-MDA5 patients revealed a high incidence of (8/11,72.7%) and different pattern from that in antibody-negative DM. MDA5, MAVS, IFN regulatory factor 7, and IFN stimulated gene 15 expression levels in the muscles of anti-MDA5 DM patients were higher than those of the controls (P < 0.05) but lower than those of antibody-negative DM patients (P < 0.05). The MAVS levels negatively correlated with manual muscle test 8 scores (r = 0.701, P = 0.016).

CONCLUSIONS:

Compared to antibody-negative DM, we presented a different distribution of the mitochondrial pathology and less severe morphology in anti-MDA5 DM. We also revealed the enhanced but less intensive MAVS-IFN1 signaling pathway activity in muscles of anti-MDA5 DM. Such disparity suggested the potentially different mechanism of muscle injury in two DM groups.

• Authors: Yanyan Jiang, Yilin Liu, Yawen Zhao, Yiming Zheng, Meng Yu, Jianwen Deng, Hongjun Hao, Wei Zhang, Zhaoxia Wang, Yun Yuan
• Journal: Annals of clinical and translational neurology (Ann Clin Transl Neurol) Vol. 8 Issue 3 Pg. 677-686 (03 2021) ISSN: 2328-9503 [Electronic] United States
• PMID: 33576578 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Chemical References

• Adaptor Proteins, Signal Transducing
• Interferon Type I
• MAVS protein, human
• IFIH1 protein, human
• Interferon-Induced Helicase, IFIH1

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Adult
• Aged
• Dermatomyositis (immunology, metabolism, pathology)
• Female
• Humans
• Interferon Type I (metabolism)
• Interferon-Induced Helicase, IFIH1 (immunology)
• Male
• Middle Aged
• Mitochondria (pathology)
• Muscle, Skeletal (metabolism)
• Retrospective Studies
• Signal Transduction (physiology)