ArticleProceedings of the National Academy of Sciences of the United States of America2020
Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Trial
- A Lineup for Next Anti-Obesity Medicines: Beyond Incretin-Based Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- ActIIR inhibition improves motor outcome and preserves muscle fibers after experimental autoimmune neuritis.Acta neuropathologica communications · 2026Article
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Deletion of fibro-adipogenic progenitors-specific follistatin impairs muscle function and accelerates skeletal muscle atrophy in obese mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- Research progress on sarcopenia in the musculoskeletal system.Bone research · 2025Review
- GDF8 and activin A blockade protects against GLP-1-induced muscle loss while enhancing fat loss in obese male mice and non-human primates.Nature communications · 2025Article
- ActRII or BMPR ligands inhibit skeletal myoblast differentiation, and BMPs promote heterotopic ossification in skeletal muscles in mice.Skeletal muscle · 2025Article
- SYISL Knockout Promotes Embryonic Muscle Development of Offspring by Modulating Maternal Gut Microbiota and Fetal Myogenic Cell Dynamics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.Science (New York, N.Y.) · 2025Article
- Reduced myotube diameter induced by combined inhibition of transforming growth factor-β type I receptors Acvr1b and Tgfbr1 is associated with enhanced β1-syntrophin expression.Journal of cellular physiology · 2024Article
- Activins and Inhibins in Cardiovascular Pathophysiology.Biomolecules · 2024Review
- Activin Signaling Pathway Specialization During Embryonic and Skeletal Muscle Development in Rainbow Trout (Oncorhynchus mykiss).Marine biotechnology (New York, N.Y.) · 2024Article
- Development of a local controlled release system for therapeutic proteins in the treatment of skeletal muscle injuries and diseases.Cell death & disease · 2024Article
- The key role of myostatin b in somatic growth in fishes derived from distant hybridization.Science China. Life sciences · 2024Article
- Human Chorionic Gonadotropin Regulates the Smad Signaling Pathway by Antagonizing TGF-β in Giant Cell Tumor of Bone.Recent patents on anti-cancer drug discovery · 2024Article
- Evaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8, and Their Binding Proteins Follistatin and Follistatin-Like Protein-3 With Dementia and Cognition.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Evaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8, and Their Binding Proteins, Follistatin and Follistatin-Like Protein-3, With Measures of Skeletal Muscle Mass, Muscle Strength, and Physical Function in Older Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Fast, multiplexable and efficient somatic gene deletions in adult mouse skeletal muscle fibers using AAV-CRISPR/Cas9.Nature communications · 2023Article
- Article
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.
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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.