ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Contribution of Necroptosis to Myofiber Death in Idiopathic Inflammatory Myopathies.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation.Frontiers in immunology · 2022Pooled it
- Immunopathogenesis of Immune-Mediated Necrotizing Myopathy: Insights Drawn from Pathological Phenotypes and Mechanistic Elaboration.Biomedicines · 2026Review
- Etiopathogenesis of Immune-Mediated Necrotizing Myopathy: A Comprehensive Review of Recent Advances.CNS neuroscience & therapeutics · 2026Review
- Convergent innate immune and regulated cell-death pathways in selected myopathies.Frontiers in immunology · 2026Review
- ZBP1 contributes to IFN-β-induced PANoptosis-related skeletal muscle cell injury in dermatomyositis.Frontiers in immunology · 2026Article
- Tyro3 upregulation is associated with muscle involvement in patients with idiopathic inflammatory myopathies.Immunologic research · 2025Article
- Idiopathic Inflammatory Myopathy-Molecular Mechanisms Underlying Its Pathogenesis and Physical Therapy Effects.International journal of molecular sciences · 2025Review
- An update on the pathogenesis of idiopathic inflammatory myopathies.Current opinion in rheumatology · 2025Review
- The emerging roles of necroptosis in skeletal muscle health and disease.Pflugers Archiv : European journal of physiology · 2024Review
- Mitochondrial defects in sporadic inclusion body myositis-causes and consequences.Frontiers in cell and developmental biology · 2024Review
- The role of ZBP1 in eccentric exercise-induced skeletal muscle necroptosis.Journal of muscle research and cell motility · 2023Article
- The role of neutrophil extracellular traps and proinflammatory damage-associated molecular patterns in idiopathic inflammatory myopathies.Clinical and experimental immunology · 2023Article
- Muscle fiber necroptosis in pathophysiology of idiopathic inflammatory myopathies and its potential as target of novel treatment strategy.Frontiers in immunology · 2023Review
- Identification of featured necroptosis-related genes and imbalanced immune infiltration in sepsisFrontiers in genetics · 2023Article
- Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy.ESC heart failure · 2022Article
- Targeting necroptosis for the treatment of myositis.Nature reviews. Rheumatology · 2022Article
- Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts.Frontiers in immunology · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMyofiber 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.
methodsWestern 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.
resultsThe 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.
conclusionThese 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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