ArticleProceedings of the National Academy of Sciences of the United States of America2017
Specific targeting of TGF-β family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 104 citations in OpenAlex.
- Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy.Muscle & nerve · 2022Trial
- Short-term treatment with high dose liraglutide improves lipid and lipoprotein profile and changes hormonal mediators of lipid metabolism in obese patients with no overt type 2 diabetes mellitus: a randomized, placebo-controlled, cross-over, double-blind clinical trial.Cardiovascular diabetology · 2019Trial
- Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.Cancer discovery · 2026Article
- Sarcopenia and Skeletal Muscle Dysfunction in Liver Cirrhosis: Clinical Perspectives of Myostatin Inhibition.Biomedicines · 2026Review
- Emerging Myostatin and Metabolic Hormone Pathway Modulators in Cardiometabolic Disease: Mechanisms, Evidence, and Therapeutic Potential.Journal of cardiovascular translational research · 2026Review
- Review
- Myostatin Inhibitory D‑Peptides Induce Skeletal Muscle Hypertrophy along with Alteration of Bioactive Sphingolipid Metabolism.ACS pharmacology & translational science · 2026Article
- Potential Influence of Myokines on Skeletal Muscle Tissue Hypertrophy Signaling Pathways: A Narrative Review.Biomolecules · 2026Review
- Pro-inflammatory cytokine-driven molecular signaling in skeletal muscle during cancer cachexia.Biochemical Society transactions · 2026Review
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus).PloS one · 2026Article
- Smad2/3 Signaling Mediates the Atrophic Response in Vocal Fold Myoblasts In Vitro.The Laryngoscope · 2026Article
- Adjuvant pharmacological strategies for the musculoskeletal system during long-term space missions.British journal of clinical pharmacology · 2026Review
- GDF10 exacerbates metastatic burden and cachexia in murine models of cancer.Frontiers in physiology · 2026Article
- Role of Peptides in Skeletal Muscle Wasting: A Scoping Review.Journal of cachexia, sarcopenia and muscle · 2025Article
- Cachexia in mice blunts improved cognitive flexibility induced by calorie restriction.Brain, behavior, and immunity · 2025Article
- Opportunities and Risks of Promoting Skin and Bone Healing via Implant Biofunctionalization of Extracellular Matrix Protein ECM1.Journal of functional biomaterials · 2025Review
- ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset (Callithrix jacchus).bioRxiv : the preprint server for biology · 2025Article
- Hyperactivation of Transforming Growth Factor-β-Activated Kinase 1 Causes Skeletal Muscle Pathology Reminiscent of Inflammatory Myopathies.The American journal of pathology · 2025Article
- Muscle in Endocrinology: From Skeletal Muscle Hormone Regulation to Myokine Secretion and Its Implications in Endocrine-Metabolic Diseases.Journal of clinical medicine · 2025Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (∼20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth. Inhibiting myostatin induced a more profound increase in muscle mass (∼45%), demonstrating a more prominent role for this ligand as a negative regulator of adult muscle mass. Remarkably, codelivery of activin and myostatin inhibitors induced a synergistic response, resulting in muscle mass increasing by as much as 150%. Transcription and protein analysis indicated that this substantial hypertrophy was associated with both the complete inhibition of the Smad2/3 pathway and activation of the parallel bone morphogenetic protein (BMP)/Smad1/5 axis (recently identified as a positive regulator of muscle mass). Analyses indicated that hypertrophy was primarily driven by an increase in protein synthesis, but a reduction in ubiquitin-dependent protein degradation pathways was also observed. In models of muscular dystrophy and cancer cachexia, combined inhibition of activins and myostatin increased mass or prevented muscle wasting, respectively, highlighting the potential therapeutic advantages of specifically targeting multiple Smad2/3-activating ligands in skeletal muscle.
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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.