CoChat
Sign Up
Cited by 512Muscle Physiology and DisordersImmune cells in cancerNeurogenetic and Muscular Disorders Research

The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.

Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy

Open access
Villalta, S. A., Nguyen, H. X., Deng, B., Gotoh, T., Tidball, J. G.·2008·Human Molecular Genetics
DOI 10.1093/hmg/ddn376PMC PMC2638796
Open this paper in CoChat — free accountOpen PDF

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/hmg/ddn376

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 60 references

Cited by

Sorted by citations

Items 401–500 of 509

Related

See all

Metadata

Authors
Villalta, S. A., Nguyen, H. X., Deng, B., Gotoh, T., & Tidball, J. G.
Affiliations
  • University of California, Los Angeles (US)
  • Kumamoto University (JP)
Corresponding author
Tidball, J. G.
ORCID
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2008-11-07
Volume
18
Issue
3
Pages
482-496
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
DOI
10.1093/hmg/ddn376
PMC
PMC2638796
OpenAlex
W2144067550
Cited by
512
References
60
Citations by year
2026: 11 · 2025: 25 · 2024: 18 · 2023: 28 · 2022: 41 · 2021: 32 · 2020: 32 · 2019: 33 · 2018: 39 · 2017: 37 · 2016: 25 · 2015: 39 · 2014: 40 · 2013: 32 · 2012: 27
FWCI
7.14
Type
journal article
Language
en
Open access
Locations
  • Human Molecular Genetics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Muscular Dystrophy Association
  • National Institutes of Health (5r01ar040343-12, AR40343)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR047855, R01 AR47721, R01 AR 40343, R01AR047721, F31AR054724)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
Keywords
Duchenne muscular dystrophy, mdx mice, macrophage polarization, M1 macrophages, M2 macrophages, arginine metabolism, arginase, inducible nitric oxide synthase, nitric oxide, muscle necrosis, muscle regeneration, IL-10, IL-4, CD163, satellite cell proliferation, tissue repair
MeSH terms
Animals, Arginine, Cells, Cultured, Humans, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Muscular Dystrophy, Animal, Nitric Oxide, Phenotype, Severity of Illness Index, Cytokines, Muscle, Skeletal, Muscular Dystrophy, Duchenne, Cell Proliferation, Mice, Nitric Oxide Synthase Type II

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review