ArticleJournal of cachexia, sarcopenia and muscle2017
Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinase.
Article in Journal of cachexia, sarcopenia and muscle, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 77 citations in OpenAlex.
- Targeting the activin/myostatin - actrii pathway to preserve skeletal muscle mass in obesity: mechanistic insights and therapeutic perspectives.Reviews in endocrine & metabolic disorders · 2026Review
- Cancer cachexia: A tumor-driven disorder of whole-body homeostasis.Cancer cell · 2026Review
- ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus).PloS one · 2026Article
- Crosstalk in the kidney-muscle axis: myokines and muscle-relevant mediators in chronic kidney disease-associated sarcopenia.Frontiers in medicine · 2026Review
- Skeletal Muscle as an Auto-, Para- and Endocrine Organ: The Role of Myokines in Muscle Metabolism and Other Metabolic Organs.Physiological research · 2025Review
- TAK-242 inhibits toll-like receptor-4 signaling and attenuates cancer-associated muscle atrophy via the p38-C/EBPβ pathway.Journal of molecular histology · 2025Article
- 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
- An alternative pocket for binding the N-degrons by the UBR1 and UBR2 ubiquitin E3 ligases.Protein science : a publication of the Protein Society · 2025Article
- Mechanically sensitive MAPK signalling mediates resistance exercise-induced muscle growth.Nature metabolism · 2025Article
- Activin A is deeply involved in the progression of sarcopenia and leads to poor prognosis in lung cancer patients.Scientific reports · 2025Article
- Activin A affects colorectal cancer progression and immunomodulation in a stage dependent manner.Scientific reports · 2025Article
- Effects of alpha-ketoisocaproate in oxidative stress-induced C2C12 myotubes via inhibition of p38 MAPK and ERK1/2.Biochemistry and biophysics reports · 2025Article
- Establishment of fracture blister model and analysis of plasma protein markers in rats.Frontiers in immunology · 2025Article
- Myostatin and Activin A as Biomarkers of Sarcopenia in Inflammatory Bowel Disease Patients.Nutrients · 2024Article
- Emerging role of TAK1 in the regulation of skeletal muscle mass.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- A New Signature of Sarcoma Based on the Tumor Microenvironment Benefits Prognostic Prediction.International journal of molecular sciences · 2023Article
- Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges.Pharmaceutics · 2023Review
- Patient-Derived Pancreatic Cancer Cells Induce C2C12 Myotube Atrophy by Releasing Hsp70 and Hsp90.Cells · 2022Article
- Cancer Cachexia and Antitumor Immunity: Common Mediators and Potential Targets for New Therapies.Life (Basel, Switzerland) · 2022Review
- Inhibition of activin A receptor signalling attenuates age-related pathological cardiac remodelling.Disease models & mechanisms · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundActivation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB-activated muscle catabolism is poorly defined.
methodsWe investigated the role of p38β mitogen-activated protein kinases (MAPK) in mediating ActRIIB ligand activin A-activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically.
resultsTreatment of C2C12 myotubes with activin A or myostatin rapidly activated p38 MAPK and its effector C/EBPβ within 1 h. Paradoxically, Akt was activated at the same time through a p38 MAPK-independent mechanism. These events were followed by up-regulation of ubiquitin ligases atrogin1 (MAFbx) and UBR2 (E3α-II), as well as increase in LC3-II, a marker of autophagosome formation, leading to myofibrillar protein loss and myotube atrophy. The catabolic effects of activin A were abolished by p38α/β MAPK inhibitor SB202190. Using small interfering RNA-mediated gene knockdown, we found that the catabolic activity of activin A was dependent on p38β MAPK specifically. Importantly, systemic administration of activin A to mice similarly activated the catabolic pathways in vivo, and this effect was blocked by SB202190. Further, activin A failed to activate the catabolic pathways in mice with muscle-specific knockout of p38β MAPK. Interestingly, activin A up-regulated MuRF1 in a p38 MAPK-independent manner, and MuRF1 did not appear responsible for activin A-induced myosin heavy chain loss and muscle atrophy.
conclusionsActRIIB-mediated activation of muscle catabolism is dependent on p38β MAPK-activated signalling.
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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.