ArticleThe Journal of pathology2013
The effects of MyD88 deficiency on disease phenotype in dysferlin-deficient A/J mice: role of endogenous TLR ligands.
Article in The Journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Comprehensive Proteomic Analysis of Dysferlinopathy Unveiling Molecular Mechanisms and Biomarkers Linked to Pathological Progression.CNS neuroscience & therapeutics · 2024Article
- Single cell RNA sequencing of human FAPs reveals different functional stages in Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2024Article
- Nano-Immunomodulation: A New Strategy for Skeletal Muscle Diseases and Aging?International journal of molecular sciences · 2023Review
- Genetic Mapping of Behavioral Traits Using the Collaborative Cross Resource.International journal of molecular sciences · 2022Article
- Inhibition of the immunoproteasome modulates innate immunity to ameliorate muscle pathology of dysferlin-deficient BlAJ mice.Cell death & disease · 2022Article
- Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies.Biomedicines · 2022Review
- Ischemia reperfusion injury provokes adverse left ventricular remodeling in dysferlin-deficient hearts through a pathway that involves TIRAP dependent signaling.Scientific reports · 2020Article
- Progressive Skeletal Muscle Atrophy in Muscular Dystrophies: A Role for Toll-like Receptor-Signaling in Disease Pathogenesis.International journal of molecular sciences · 2020Review
- Fibroadipogenic progenitors are responsible for muscle loss in limb girdle muscular dystrophy 2B.Nature communications · 2019Article
- MyD88 is required for satellite cell-mediated myofiber regeneration in dystrophin-deficient mdx mice.Human molecular genetics · 2018Article
- Immunobiology of Inherited Muscular Dystrophies.Comprehensive Physiology · 2018Review
- MyD88 promotes myoblast fusion in a cell-autonomous manner.Nature communications · 2017Article
- Coupling of excitation to CaThe Journal of physiology · 2017Article
- Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle.Human molecular genetics · 2017Article
- Toll-like receptor signalling in regenerative myogenesis: friend and foe.The Journal of pathology · 2016Article
- Myofiber damage precedes macrophage infiltration after in vivo injury in dysferlin-deficient A/J mouse skeletal muscle.The American journal of pathology · 2015Article
- Toll-like receptor 4 ablation in mdx mice reveals innate immunity as a therapeutic target in Duchenne muscular dystrophy.Human molecular genetics · 2015Article
- The effects of H3N2 swine influenza virus infection on TLRs and RLRs signaling pathways in porcine alveolar macrophages.Virology journal · 2015Article
- Upregulated IL-1β in dysferlin-deficient muscle attenuates regeneration by blunting the response to pro-inflammatory macrophages.Skeletal muscle · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
Abstract
An absence of dysferlin leads to activation of innate immune receptors such as Toll-like receptors (TLRs) and skeletal muscle inflammation. Myeloid differentiation primary response gene 88 (MyD88) is a key mediator of TLR-dependent innate immune signalling. We hypothesized that endogenous TLR ligands released from the leaking dysferlin-deficient muscle fibres engage TLRs on muscle and immune cells and contribute to disease progression. To test this hypothesis, we generated and characterized dysferlin and MyD88 double-deficient mice. Double-deficient mice exhibited improved body weight, grip strength, and maximum muscle contractile force at 6-8 months of age when compared to MyD88-sufficient, dysferlin-deficient A/J mice. Double-deficient mice also showed a decrease in total fibre number, which contributed to the observed increase in the number of central nuclei/fibres. These results indicate that there was less regeneration in the double-deficient mice. We next tested the hypothesis that endogenous ligands, such as single-stranded ribonucleic acids (ssRNAs), released from damaged muscle cells bind to TLR-7/8 and perpetuate the disease progression. We found that injection of ssRNA into the skeletal muscle of pre-symptomatic mice (2 months old) resulted in a significant increase in degenerative fibres, inflammation, and regenerating fibres in A/J mice. In contrast, characteristic histological features were significantly decreased in double-deficient mice. These data point to a clear role for the TLR pathway in the pathogenesis of dysferlin deficiency and suggest that TLR-7/8 antagonists may have therapeutic value in this disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.