Downregulation of the NLRP3 inflammasome by adiponectin rescues Duchenne muscular dystrophy
Open accessAbstract
BACKGROUND: The hormone adiponectin (ApN) exerts powerful anti-inflammatory effects on skeletal muscle and can reverse devastating myopathies, like Duchenne muscular dystrophy (DMD), where inflammation exacerbates disease progression. The NLRP3 inflammasome plays a key role in the inflammation process, and its aberrant activation leads to several inflammatory or immune diseases. Here we investigated the expression of the NLRP inflammasome in skeletal muscle and its contribution to DMD. RESULTS: We find that NLRP3 is expressed in skeletal muscle and show that ApN downregulates NLRP3 via its anti-inflammatory mediator, miR-711. This repression occurs both in vitro in C2C12 myotubes and in vivo after either local (via muscle electrotransfer) or systemic (by using transgenic mice) ApN supplementation. To explore the role of the NLRP3 inflammasome in a murine model of DMD, we crossed mdx mice with Nlrp3-knockout mice. In mdx mice, all components of the inflammasome were upregulated in muscle, and the complex was overactivated. By contrast, in mdx mice lacking Nlrp3, there was a reduction in caspase-1 activation, inflammation and oxidative stress in dystrophic muscle, and these mice showed higher global muscle force/endurance than regular mdx mice as well as decreased muscle damage. To investigate the relevance of NLPR3 regulation in a human disease context, we characterized NLRP3 expression in primary cultures of myotubes from DMD subjects and found a threefold increase compared to control subjects. This overexpression was attenuated by ApN or miR-711 mimic treatments. CONCLUSIONS: The NLRP3 inflammasome plays a key pathogenic role in DMD and muscle inflammation, thereby opening new therapeutic perspectives for these and other related disorders.
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miR-711 can repress NF-κB and NLRP3 inflammasome activation.
“Indeed, miR-711 can repress NF-κB and NLRP3 inflammasome activation [63].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [63]
NLRP3 was up-regulated in mdx mice but was then normalized in mdx-ApN mice, through miR-711 expression.
“NLRP3 was up-regulated in mdx mice but was then normalized in mdx-ApN mice, through miR-711 expression [63].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [63]
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- Authors
- Boursereau, R., Abou-Samra, M., Lecompte, S., Noel, L., & Brichard, S. M.
- Affiliations
- UCLouvain (BE)
- Corresponding author
- Brichard, Sonia M.
- Venue
- BMC Biology
- Published
- 2018-03-20
- Volume
- 16
- Issue
- 1
- Pages
- 33-33
- ISSN
- 1741-7007 (ISSN-L)
- PMC
- PMC5861675
- OpenAlex
- W2804669464
- Cited by
- 72
- References
- 39
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 14 · 2022: 13 · 2021: 12 · 2020: 5 · 2019: 8 · 2018: 2
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Actions de recherche concertée (ARC 12 -17/047)
- Fonds De La Recherche Scientifique - FNRS (1.5097.12, T.0212.13)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Epidemiology › Inflammatory Myopathies and Dermatomyositis
- Keywords
- Duchenne muscular dystrophy, NLRP3 inflammasome, adiponectin, muscle inflammation, caspase-1 activation, oxidative stress, mdx mice, skeletal muscle, anti-inflammatory therapy, muscle damage
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Cell Line, Cells, Cultured, Humans, Immunohistochemistry, Male, Blotting, Western, Mice, Knockout, Muscle, Skeletal, Muscular Dystrophy, Duchenne, MicroRNAs, Mice, Adiponectin, Inflammasomes
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