ArticleAnnals of translational medicine2020
Inhibition of IL-6/JAK/STAT3 pathway rescues denervation-induced skeletal muscle atrophy.
Article in Annals of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 107 citations in OpenAlex.
- JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle.Life science alliance · 2024Trial
- Peripheral Nerve Injury and Denervation-Induced Sarcopenia with a Focus on Pharmacological Dual-Target Strategies.Biomolecules & therapeutics · 2026Review
- A bioengineered platform reveals progressive impairment of skeletal muscles by metabolic dysfunction-associated steatotic liver disease-derived factors.Disease models & mechanisms · 2026Article
- RIPK3 Inhibition Mitigates Denervated Muscle Atrophy via NOX4-Mediated Mitochondrial Restoration and Inflammation Suppression.Journal of cachexia, sarcopenia and muscle · 2026Article
- The Dual Role of Interleukin-6 in the Pathophysiology of Skeletal Muscle: Mechanisms, Challenges, and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Scutellarein attenuates cancer cachexia-induced muscle atrophy via targeted inhibition of the JAK/STAT pathway.Journal of advanced research · 2026Article
- Mitochondrial Impairment in Unloaded Postural Muscle: Mechanisms Driving Loss of Muscle Function and Mass.Antioxidants (Basel, Switzerland) · 2026Review
- NF-κB Signaling as a Central Driver of Cancer Cachexia.Cancers · 2026Review
- Fos-induced osteosarcoma growth causes a cachexia-like phenotype in mice and correlates with high Fgf21 serum levels.Cancer & metabolism · 2026Article
- The SIRT1/STAT3 axis as a central regulator of immune, inflammatory, and lipid metabolic dysregulation in rheumatoid arthritis: therapeutic implications.Frontiers in immunology · 2026Review
- IL-6 signaling orchestrates proteolytic hubs MuRF1 and Atrogin-1 in NSCLC induced sarcopenia.Frontiers in immunology · 2026Article
- Spatial-Bioenergetic-Immune Axis in Type 2 Diabetes Mellitus-Associated Sarcopenia: A Review from Pathogenesis to Targeted Reconstruction.Journal of inflammation research · 2026Review
- Causal association and molecular mechanisms of periodontal disease and muscle wasting and atrophy: Mendelian randomization and bioinformatics analysis.Frontiers in genetics · 2026Article
- Myosteatosis: Epidemiological Insights, Functional Decline, and Diagnostic Advances.Current obesity reports · 2025Review
- Association of serological biomarkers with muscle strength and function in sarcopenia: a cross-sectional study.Annals of medicine · 2025Article
- Immune-mediated interactions between sarcopenia and atherosclerosis in aging.Immunity & ageing : I & A · 2025Review
- Cisplatin-Induced Skeletal Muscle Atrophy: Biomolecular Mechanisms and the Protective Role of Exercise-Induced Myokines.Biomolecules · 2025Review
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- Temporal dynamics and functional implications of MiRNAs in denervation-induced skeletal muscle atrophy.Molecular biology reports · 2025Article
- Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice.Aging · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe molecular mechanisms underlying denervated skeletal muscle atrophy with concomitant muscle mass loss have not been fully elucidated. Therefore, this study aimed to attain a deeper understanding of the molecular mechanisms underlying denervated skeletal muscle atrophy as a critical step to developing targeted therapy and retarding the concomitant loss of skeletal muscle mass.
methodsWe employed microarray analysis to reveal the potential molecular mechanisms underlying denervated skeletal muscle atrophy. We used
resultsIn this study, microarray analysis of the differentially expressed genes demonstrated that inflammation-related cytokines were markedly triggered and IL-6/JAK/STAT3 signaling pathway was strongly activated during denervated skeletal muscle atrophy. The high level of IL-6 enhanced C2C12 myotube atrophy through the activation of JAK/STAT3, while inhibiting JAK/STAT3 pathway by ruxolitinib (a JAK1/2 inhibitor) or C188-9 (a STAT3 inhibitor) significantly attenuated C2C12 myotube atrophy induced by IL-6. Pharmacological blocking of IL-6 by tocilizumab (antibody against IL-6 receptor) and pharmacological/genetic inhibition of JAK/STAT3 pathway by ruxolitinib/C188-9 (JAK/STAT3 inhibitor) and STAT3 short hairpin RNA (shRNA) lentivirus in tibialis anterior muscles could suppress muscle atrophy and inhibit mitophagy, and was accompanied by the decreased expression of atrophic genes (
conclusionsTaken together, the results suggest that IL-6/JAK/STAT3 pathway may be a principal mediator in denervated skeletal muscle atrophy, meaning targeted therapy against IL-6/JAK/STAT3 pathway might have potential as a therapeutic strategy for prevention of skeletal muscle atrophy.
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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.