Aberrant Expression of High Mobility Group Box Protein 1 in the Idiopathic Inflammatory Myopathies

Day, Jessica; Otto, Sophia; Cash, Kathy; Eldi, Preethi; Hissaria, Pravin; Proudman, Susanna; Limaye, Vidya; Hayball, John D.

doi:10.3389/fcell.2020.00226

Cited by 13 publications

(12 citation statements)

References 37 publications

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“…Additional in vitro studies have demonstrated that HMGB1 can accelerate muscle fatigue and induce major histocompatibility complex class I expression in muscle fibers by interacting with its receptor, Toll‐like receptor 4 (34). More recently, Day et al showed that sarcoplasmic HMGB1 expression correlated with muscle weakness and histologic myonecrosis, inflammation, regeneration, and autophagy in patients with IIM (35). In the present study, we found similar patterns of HMGB1 expression in the muscle tissue of patients with IIM.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Necroptosis to Myofiber Death in Idiopathic Inflammatory Myopathies

Peng

Zhang

Liang

et al. 2022

Arthritis & Rheumatology

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Objective Myofiber necrosis is a significant pathologic characteristic of idiopathic inflammatory myopathies (IIMs), and its molecular mechanism is largely unknown. Necroptosis is a recently identified form of regulated necrotic cell death, and its activation might have crucial biologic consequences. The aim of the present study was to investigate the role of necroptosis in IIM muscle damage. Methods Western blot and immunohistochemistry analyses were performed to examine the expression of receptor‐interacting protein 3 (RIP‐3) and mixed‐lineage kinase domain–like (MLKL) proteins in 26 IIM patients and 4 healthy controls, as well as necroptosis‐related damage–associated molecular pattern molecules. Tumor necrosis factor (TNF) was used to stimulate cultured C2C12 myoblasts, and the involvement of necroptosis in cell death of C2C12 cells was studied in vitro. Results The expression of RIP‐3 and MLKL proteins and their phosphorylated forms was significantly increased in the muscle tissue of IIM patients compared to that of healthy controls. The expression levels of RIP‐3 and MLKL proteins were associated with the severity of muscle damage in patients with IIM. Significant colocalization of MLKL with high mobility group box chromosomal protein 1 in necrotizing myofibers was observed in muscle biopsy tissue from patients with IIM. Stimulation of C2C12 myoblasts with TNF and a pan‐caspase inhibitor, Z‐VAD, resulted in the overactivation of necroptosis and significantly increased necrotic cell death. Strategies involving either inhibition of necroptosis with necrostatin‐1 or knockdown of MLKL expression successfully prevented necroptosis‐induced cell death of C2C12 cells. Conclusion These findings demonstrate that overactivated necroptosis contributes to muscle damage in IIMs and suggest that necroptosis inhibitors could represent a new therapeutic target in the treatment of IIMs.

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Section: Discussionmentioning

confidence: 99%

Contribution of Necroptosis to Myofiber Death in Idiopathic Inflammatory Myopathies

Peng

Zhang

Liang

et al. 2022

Arthritis & Rheumatology

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“…It is well established that autoimmune and inflammation response, to a great extent, contribute to the pathogenesis of IIM. Current research for the pathophysiology of IIM has mainly focused on immune and inflammatory response, such as autoantibodies ( Benveniste et al, 2016 ; Arouche-Delaperche et al, 2017 ; Darnoiseaux et al, 2019 ), complement ( Allenbach, Arouche-Delaperche et al, 2018 ; Bergua et al, 2019 ), cytokines ( Day et al, 2020 ), inflammatory cells ( Preuße et al, 2012 ; Rinnenthal et al, 2014 ; Knauss et al, 2019 ; Jiang et al, 2020 ; Seto et al, 2020 ), interferon-signature ( Greenberg et al, 2005 ; Gallay et al, 2019 ), and the upregulation of major histocompatibility complex—class I on myofibers ( Bhattarai et al, 2016 ; Wang et al, 2018 ). Although a previous study revealed evidence for activation of the ER stress response in polymyositis and DM ( Nagaraju et al, 2005 ; Alger et al, 2011 ), the functional role of ER stress was still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies

Gao

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Objectives: Endoplasmic reticulum (ER) stress plays pivotal roles in the regulation of skeletal muscle damage and dysfunction in multiple disease conditions. We postulate the activation of ER stress in idiopathic inflammatory myopathies (IIM).Methods: Thirty-seven patients with immune-mediated necrotizing myopathy (IMNM), 21 patients with dermatomyositis (DM), 6 patients with anti-synthetase syndrome (ASS), and 10 controls were enrolled. The expression of ER stress-induced autophagy pathway was detected using histological sections, Western blot, and real-time quantitative Polymerase Chain Reaction.Results: ER stress-induced autophagy pathway was activated in biopsied muscle of patients with IMNM, DM, and ASS. The ER chaperone protein, glucose-regulated protein 78 (GRP78)/BiP expression in skeletal muscle correlated with autophagy, myofiber atrophy, myonecrosis, myoregeneration, and disease activity in IMNM.Conclusion: ER stress was involved in patients with IIM and correlates with disease activity in IMNM. ER stress response may be responsible for skeletal muscle damage and repair in IIM.

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“…Furthermore, infiltration of lymphocytes expressing Bcl-2 and betachemokine receptor 4 (CCR4) (both negatively affected by statins) seemed to be a marker of anti-HMGCR+ IMNM (29). The High Mobility Group Box Protein 1 (HMGB1, a DNA-binding acting as a damage signal and pro-inflammatory mediator) was also overexpressed in IIMs muscle samples and serum, especially in IMNM (30). Moreover, Day et al (31) demonstrated that IMNM samples from different patients may display different degree of necrosis and that the amount of myofibre complement deposition was closely associated with clinical severity.…”

Section: Review Idiopathic Inflammatory Myopathies: One Year In Revie...mentioning

confidence: 99%

Idiopathic inflammatory myopathies: one year in review 2021

Cardelli

Zanframundo

Cometi

et al. 2022

Clinical and Experimental Rheumatology

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Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare and complex connective tissue diseases, mainly characterised by inflammatory involvement of skeletal muscles. Several other organs may be affected, particularly lungs, heart, skin, gastrointestinal tract and joints, often determining the morbidity and mortality associated with these autoimmune disorders. The course is generally chronic and the onset subacute. This latter aspect, together with the rarity of these conditions, can result in a clinical challenge for the physician with a considerable diagnostic delay. The scientific literature makes continuous advances in the understanding of these diseases, in particular with regards to the pathogenesis, serological findings, diagnostic strategies and therapeutic approaches. The aim of this review is to highlight the most relevant literature contributions published on this topic over the last year.

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Aberrant Expression of High Mobility Group Box Protein 1 in the Idiopathic Inflammatory Myopathies

Cited by 13 publications

References 37 publications

Contribution of Necroptosis to Myofiber Death in Idiopathic Inflammatory Myopathies

Contribution of Necroptosis to Myofiber Death in Idiopathic Inflammatory Myopathies

Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies

Idiopathic inflammatory myopathies: one year in review 2021

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