ArticleThe Journal of biological chemistry2016
Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- Inactivation of SERCA2 at Cys674 induces skeletal muscle atrophy by activating the TGFβ/Smad-S100a4 axis to promote inflammation.Redox biology · 2026Article
- Targeting the activin/myostatin - actrii pathway to preserve skeletal muscle mass in obesity: mechanistic insights and therapeutic perspectives.Reviews in endocrine & metabolic disorders · 2026Review
- SMAD2 ubiquitination through PY motif regulates skeletal muscle mass and fibrotic degeneration.Scientific reports · 2026Article
- LEM-Domain-Containing Inner Nuclear Membrane Proteins: Emerging Regulators of Intranuclear Signaling.International journal of molecular sciences · 2026Review
- Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- A Single Intraperitoneal Secreted Protein Acidic and Rich in Cysteine Injection in Mice Is Towards an Exercise-like Phenotype.Biology · 2025Article
- The Loss of HJV Aggravates Muscle Atrophy by Promoting the Activation of the TβRII/Smad3 Pathway.International journal of molecular sciences · 2025Article
- The Effect of Anti-Activin Receptor Type IIA and Type IIB Antibody on Muscle, Bone and Blood in Healthy and Osteosarcopenic Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Article
- Effects of hindlimb unloading on the mevalonate and mechanistic target of rapamycin complex 1 signaling pathways in a fast-twitch muscle in rats.Physiological reports · 2024Article
- The mechanosensitive geneAmerican journal of physiology. Cell physiology · 2024Article
- Bezafibrate attenuates immobilization-induced muscle atrophy in mice.Scientific reports · 2024Article
- Association of a variant upstream ofTranslational animal science · 2023Article
- Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-β via Smad3 acetylation.Nature communications · 2022Article
- Article
- The role of the Smad2/3/4 signaling pathway in osteogenic differentiation regulation by ClC-3 chloride channels in MC3T3-E1 cells.Journal of orthopaedic surgery and research · 2022Article
- Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p.Bioengineered · 2022Article
- Methylglyoxal Induces Inflammation, Metabolic Modulation and Oxidative Stress in Myoblast Cells.Toxins · 2022Article
- Shared and distinct mechanisms of skeletal muscle atrophy: A narrative review.Ageing research reviews · 2021Review
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes.
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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.