ArticleHuman molecular genetics2011
SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Pooled it
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- Reducing the Excess Activin Signaling Rescues Muscle Degeneration in Myotonic Dystrophy Type 2Journal of personalized medicine · 2022Article
- Dilated cardiomyopathy: a new insight into the rare but common cause of heart failure.Heart failure reviews · 2022Review
- Effects of chronic hypoxia on the gene expression profile in the embryonic heart in three Chinese indigenous chicken breeds (Frontiers in veterinary science · 2022Article
- 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
- Glucagon-like peptide-1 receptor and sarcoglycan delta genetic variants can affect cardiovascular risk in chronic kidney disease patients under hemodialysis.Clinical kidney journal · 2020Article
- Maintenance of the Undifferentiated State in Myogenic Progenitor Cells by TGFβ Signaling is Smad Independent and Requires MEK Activation.International journal of molecular sciences · 2020Article
- Article
- Therapeutic strategies for preventing skeletal muscle fibrosis after injury.Frontiers in pharmacology · 2015Review
- Excess SMAD signaling contributes to heart and muscle dysfunction in muscular dystrophy.Human molecular genetics · 2014Article
- Silencing of drpr leads to muscle and brain degeneration in adult Drosophila.The American journal of pathology · 2014Article
- Modifying muscular dystrophy through transforming growth factor-β.The FEBS journal · 2013Review
- Pharmacological inhibition of myostatin/TGF-β receptor/pSmad3 signaling rescues muscle regenerative responses in mouse model of type 1 diabetes.Acta pharmacologica Sinica · 2013Article
- LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy.Annals of neurology · 2013Article
- Formin homology 2 domain containing 3 variants associated with hypertrophic cardiomyopathy.Circulation. Cardiovascular genetics · 2013Article
- Takotsubo Cardiomyopathy following a L2-L5 Laminectomy and Fusion In Situ with Bone Morphogenic Protein.Case reports in orthopedics · 2013Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Loss-of-function mutations in the genes encoding dystrophin and the associated membrane proteins, the sarcoglycans, produce muscular dystrophy and cardiomyopathy. The dystrophin complex provides stability to the plasma membrane of striated muscle during muscle contraction. Increased SMAD signaling due to activation of the transforming growth factor-β (TGFβ) pathway has been described in muscular dystrophy; however, it is not known whether this canonical TGFβ signaling is pathogenic in the muscle itself. Drosophila deleted for the γ/δ-sarcoglycan gene (Sgcd) develop progressive muscle and heart dysfunction and serve as a model for the human disorder. We used dad-lacZ flies to demonstrate the signature of TGFβ activation in response to exercise-induced injury in Sgcd null flies, finding that those muscle nuclei immediately adjacent to muscle injury demonstrate high-level TGFβ signaling. To determine the pathogenic nature of this signaling, we found that partial reduction of the co-SMAD Medea, homologous to SMAD4, or the r-SMAD, Smox, corrected both heart and muscle dysfunction in Sgcd mutants. Reduction in the r-SMAD, MAD, restored muscle function but interestingly not heart function in Sgcd mutants, consistent with a role for activin but not bone morphogenic protein signaling in cardiac dysfunction. Mammalian sarcoglycan null muscle was also found to exhibit exercise-induced SMAD signaling. These data demonstrate that hyperactivation of SMAD signaling occurs in response to repetitive injury in muscle and heart. Reduction of this pathway is sufficient to restore cardiac and muscle function and is therefore a target for therapeutic reduction.
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Registered trials
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