ArticleHuman molecular genetics2014
Excess SMAD signaling contributes to heart and muscle dysfunction in muscular dystrophy.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- The D2.B10-DmdThe American journal of pathology · 2026Article
- A genetic variant inScience advances · 2025Article
- HDAC inhibitors as pharmacological treatment for Duchenne muscular dystrophy: a discovery journey from bench to patients.Trends in molecular medicine · 2024Review
- Intrapericardial long non-coding RNA-Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair.European heart journal · 2023Article
- Genetic Disruption of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Triggers Differential Cardiac Fibrosis and Disorders in Male and Female Mutant Mice: Role of TGF-β1/SMAD Signaling Pathway.International journal of molecular sciences · 2022Article
- X-linked myotubular myopathy is associated with epigenetic alterations and is ameliorated by HDAC inhibition.Acta neuropathologica · 2022Article
- Transforming growth factor β1 impairs the transcriptomic response to contraction in myotubes from women with polycystic ovary syndrome.The Journal of physiology · 2022Article
- Reducing the Excess Activin Signaling Rescues Muscle Degeneration in Myotonic Dystrophy Type 2Journal of personalized medicine · 2022Article
- Anti-latent TGFβ binding protein 4 antibody improves muscle function and reduces muscle fibrosis in muscular dystrophy.Science translational medicine · 2021Article
- Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina.PloS one · 2021Article
- Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy.International journal of molecular sciences · 2020Review
- Is Mitochondrial Oxidative Stress the Key Contributor to Diaphragm Atrophy and Dysfunction in Critically Ill Patients?Critical care research and practice · 2020Review
- Molecular Mechanisms Mediating Adaptation to Exercise.Advances in experimental medicine and biology · 2020Review
- Genetic manipulation of CCN2/CTGF unveils cell-specific ECM-remodeling effects in injured skeletal muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Cardiomyocyte SMAD4-Dependent TGF-β Signaling is Essential to Maintain Adult Heart Homeostasis.JACC. Basic to translational science · 2019Article
- Article
- Treating pediatric neuromuscular disorders: The future is now.American journal of medical genetics. Part A · 2018Review
- Smad3 initiates oxidative stress and proteolysis that underlies diaphragm dysfunction during mechanical ventilation.Scientific reports · 2017Article
- Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury.PLoS genetics · 2017Article
- The expression of Smad signaling pathway in myocardium and potential therapeutic effects.Histology and histopathology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Disruption of the dystrophin complex causes muscle injury, dysfunction, cell death and fibrosis. Excess transforming growth factor (TGF) β signaling has been described in human muscular dystrophy and animal models, where it is thought to relate to the progressive fibrosis that characterizes dystrophic muscle. We now found that canonical TGFβ signaling acutely increases when dystrophic muscle is stimulated to contract. Muscle lacking the dystrophin-associated protein γ-sarcoglycan (Sgcg null) was subjected to a lengthening protocol to produce maximal muscle injury, which produced rapid accumulation of nuclear phosphorylated SMAD2/3. To test whether reducing SMAD signaling improves muscular dystrophy in mice, we introduced a heterozygous mutation of SMAD4 (S4) into Sgcg mice to reduce but not ablate SMAD4. Sgcg/S4 mice had improved body mass compared with Sgcg mice, which normally show a wasting phenotype similar to human muscular dystrophy patients. Sgcg/S4 mice had improved cardiac function as well as improved twitch and tetanic force in skeletal muscle. Functional enhancement in Sgcg/S4 muscle occurred without a reduction in fibrosis, suggesting that intracellular SMAD4 targets may be important. An assessment of genes differentially expressed in Sgcg muscle focused on those encoding calcium-handling proteins and responsive to TGFβ since this pathway is a target for mediating improvement in muscular dystrophy. These data demonstrate that excessive TGFβ signaling alters cardiac and muscle performance through the intracellular SMAD pathway.
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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.