The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Denervation-activated STAT3–IL-6 signalling in fibro-adipogenic progenitors promotes myofibres atrophy and fibrosis
Open accessAbstract
Fibro-adipogenic progenitors (FAPs) are typically activated in response to muscle injury, and establish functional interactions with inflammatory and muscle stem cells (MuSCs) to promote muscle repair. We found that denervation causes progressive accumulation of FAPs, without concomitant infiltration of macrophages and MuSC-mediated regeneration. Denervation-activated FAPs exhibited persistent STAT3 activation and secreted elevated levels of IL-6, which promoted muscle atrophy and fibrosis. FAPs with aberrant activation of STAT3-IL-6 signalling were also found in mouse models of spinal cord injury, spinal muscular atrophy, amyotrophic lateral sclerosis (ALS) and in muscles of ALS patients. Inactivation of STAT3-IL-6 signalling in FAPs effectively countered muscle atrophy and fibrosis in mouse models of acute denervation and ALS (SOD G93A mice). Activation of pathogenic FAPs following loss of integrity of neuromuscular junctions further illustrates the functional versatility of FAPs in response to homeostatic perturbations and suggests their potential contribution to the pathogenesis of neuromuscular diseases.
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“The FAPs in denervated muscles activate an inflammatory response program and become the most abundant source of IL6.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [87]
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“Consequently, the IL6-STAT3 axis is activated both in FAPs and myofibers leading to atrophy87 (Fig. 5).”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [87]
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Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis
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Interleukin-6 Is an Essential Regulator of Satellite Cell-Mediated Skeletal Muscle Hypertrophy
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Type 2 Innate Signals Stimulate Fibro/Adipogenic Progenitors to Facilitate Muscle Regeneration
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Regulation of Muscle Growth and Regeneration by the Immune System
Tidball, J. G. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.150 · Cited by 740
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Metadata
- Authors
- Madaro, L., Passafaro, M., Sala, D., Etxaniz, U., Lugarini, F., Proietti, D., Alfonsi, M. V., Nicoletti, C., Gatto, S., De Bardi, M., Rojas-García, R., Giordani, L., Marinelli, S., Pagliarini, V., Sette, C., Sacco, A., & Puri, P. L.
- Affiliations
- Fondazione Santa Lucia (IT)
- University of Rome Tor Vergata (IT)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Centre National de la Recherche Scientifique (FR)
- National Research Council (IT)
- Università Cattolica del Sacro Cuore (IT)
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2018-07-26
- Volume
- 20
- Issue
- 8
- Pages
- 917-927
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC6145844
- OpenAlex
- W2883365705
- Cited by
- 310
- References
- 41
- Citations by year
- 2026: 40 · 2025: 37 · 2024: 57 · 2023: 36 · 2022: 43 · 2021: 41 · 2020: 36 · 2019: 18 · 2018: 2
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-02-07)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Medical University of South Carolina
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052779, R01AR064873, P30AR061303, R01AR056712)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- fibro-adipogenic progenitors, denervation, muscle atrophy, muscle fibrosis, amyotrophic lateral sclerosis, spinal cord injury, spinal muscular atrophy, muscle regeneration, muscle stem cells, neuromuscular disorders
- MeSH terms
- Superoxide Dismutase-1, Interleukin-6 Inhibitors, Amyotrophic Lateral Sclerosis, Animals, Cell Line, Denervation, Disease Models, Animal, Fibrosis, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Muscular Atrophy, Muscular Atrophy, Spinal, Mutation, Neuromuscular Agents, Sciatic Nerve, Spinal Cord Injuries, Signal Transduction, Interleukin-6, Coculture Techniques, Myoblasts, Skeletal, Adipogenesis, STAT3 Transcription Factor, Quadriceps Muscle, Cardiotoxins
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