ArticleHuman molecular genetics2009
Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers, 3 of them syntheses that pooled it.
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Who cites it
291 citing papers in PubMed, 3 syntheses or guidelines pooled it, 508 citations in OpenAlex.
- Pooled it
- What Is the Optimal Timing of Transplantation of Neural Stem Cells in Spinal Cord Injury? A Systematic Review and Network Meta-Analysis Based on Animal Studies.Frontiers in immunology · 2022Pooled it
- Pooled it
- Electroacupuncture at ST-36 Protects Interstitial Cells of Cajal via Sustaining Heme Oxygenase-1 Positive M2 Macrophages in the Stomach of Diabetic Mice.Oxidative medicine and cellular longevity · 2018Trial
- Mesenchymal Stromal Cell-Mediated Intercellular Communication: Mapping the Interactome for Skeletal Muscle Homeostasis and Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systemic regeneration medicines for muscular dystrophy: progress and challenges in pro-regenerative drug development.Cell regeneration (London, England) · 2026Review
- Macrophage and fibro-adipogenic progenitor communication in skeletal muscle regeneration: tissue homeostasis and pathogenic remodeling.Journal of leukocyte biology · 2026Review
- Identification of biomarkers associated with pathological dynamic progression in dystrophinopathies.Scientific reports · 2026Article
- TWEAK-induced alternative NF-κB signaling regulates Cxcl10 and Mymx to promote myoblast-to-myotube fusion and muscle regeneration.Communications biology · 2026Article
- Voluntary running sustains the correction of inflammation-related gene expression conferred by AAV gene therapy in mdx mice.Molecular therapy. Advances · 2026Article
- Genetic depletion of the early autophagy protein ATG13 impairs mitochondrial energy metabolism, augments oxidative stress, induces the polarization of macrophages to the M1 inflammatory mode, and compromises myelin integrity in skeletal muscle.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Unravelling the Complications of Dilated Cardiomyopathy in Duchenne Muscular Dystrophy: From Molecular Pathways to Disease Management.Cardiovascular & hematological disorders drug targets · 2026Review
- Reprogramming brain-resident macrophages: from disease drivers to therapeutic allies in neurological disorders.Frontiers in cellular neuroscience · 2026Review
- TIM-4International journal of biological sciences · 2026Article
- When barriers fail: the role of endothelial dysfunction in rare pediatric neuromuscular diseases.Frontiers in medicine · 2026Review
- FAP-CAR-T cells reduce dystrophic muscle fibrosis, improving adeno-associated virus gene transfer efficacy.Molecular therapy. Methods & clinical development · 2025Article
- Failure to resolve inflammation contributes to juvenile onset cardiac damage in a mouse model of Duchenne muscular dystrophy.Cell death & disease · 2025Article
- Macrophage-derived Spp1 promotes intramuscular fat in dystrophic muscle.JCI insight · 2025Article
- Profiles of Monocyte Subsets and Fibrosis-Related Genes in Patients with Muscular Dystrophy Undergoing Intermittent Prednisone Therapy.International journal of molecular sciences · 2025Article
- Anti-fibrotic, muscle-promoting antibody-drug conjugates for the improvement and treatment of DMD.iScience · 2025Article
231 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
Abstract
Duchenne muscular dystrophy (DMD) is the most common, lethal, muscle-wasting disease of childhood. Previous investigations have shown that muscle macrophages may play an important role in promoting the pathology in the mdx mouse model of DMD. In the present study, we investigate the mechanism through which macrophages promote mdx dystrophy and assess whether the phenotype of the macrophages changes between the stage of peak muscle necrosis (4 weeks of age) and muscle regeneration (12 weeks). We find that 4-week-old mdx muscles contain a population of pro-inflammatory, classically activated M1 macrophages that lyse muscle in vitro by NO-mediated mechanisms. Genetic ablation of the iNOS gene in mdx mice also significantly reduces muscle membrane lysis in 4-week-old mdx mice in vivo. However, 4-week mdx muscles also contain a population of alternatively activated, M2a macrophages that express arginase. In vitro assays show that M2a macrophages reduce lysis of muscle cells by M1 macrophages through the competition of arginase in M2a cells with iNOS in M1 cells for their common, enzymatic substrate, arginine. During the transition from the acute peak of mdx pathology to the regenerative stage, expression of IL-4 and IL-10 increases, either of which can deactivate the M1 phenotype and promote activation of a CD163+, M2c phenotype that can increase tissue repair. Our findings further show that IL-10 stimulation of macrophages activates their ability to promote satellite cell proliferation. Deactivation of the M1 phenotype is also associated with a reduced expression of iNOS, IL-6, MCP-1 and IP-10. Thus, these results show that distinct subpopulations of macrophages can promote muscle injury or repair in muscular dystrophy, and that therapeutic interventions that affect the balance between M1 and M2 macrophage populations may influence the course of muscular dystrophy.
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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.