ArticleHuman molecular genetics2014
P38α MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Chronic activation of p38α in skeletal muscle causes necrotic changes, but also abolishes expression of MK2, MK3, and MKK6 and the muscle recovers.The Journal of biological chemistry · 2026Article
- Fatigue Resistance and Mitochondrial Adaptations to Isometric Interval Training in Dystrophin-Deficient Muscle: Role of Contractile Load.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Inhibition of miR-25 ameliorates cardiac and skeletal muscle dysfunction in agedMolecular therapy. Nucleic acids · 2024Article
- Muscle: an independent contributor to the neuromuscular spinal muscular atrophy disease phenotype.JCI insight · 2023Review
- Article
- Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Inhibition of the immunoproteasome modulates innate immunity to ameliorate muscle pathology of dysferlin-deficient BlAJ mice.Cell death & disease · 2022Article
- Mineralocorticoid receptor antagonists and glucocorticoids differentially affect skeletal muscle inflammation and pathology in muscular dystrophy.JCI insight · 2022Article
- Prolonged FOS activity disrupts a global myogenic transcriptional program by altering 3D chromatin architecture in primary muscle progenitor cells.Skeletal muscle · 2022Article
- Skeletal muscle-specific overexpression of miR-486 limits mammary tumor-induced skeletal muscle functional limitations.Molecular therapy. Nucleic acids · 2022Article
- Depletion of skeletal muscle satellite cells attenuates pathology in muscular dystrophy.Nature communications · 2022Article
- FSHD Therapeutic Strategies: What Will It Take to Get to Clinic?Journal of personalized medicine · 2022Review
- Fibroblasts orchestrate cellular crosstalk in the heart through the ECM.Nature cardiovascular research · 2022Article
- Analysis of Long Noncoding RNAs-Related Regulatory Mechanisms in Duchenne Muscular Dystrophy Using a Disease-Related lncRNA-mRNA Pathway Network.Genetics research · 2022Article
- p38 MAPKs - roles in skeletal muscle physiology, disease mechanisms, and as potential therapeutic targets.JCI insight · 2021Review
- Review
- Regulators of cardiac fibroblast cell state.Matrix biology : journal of the International Society for Matrix Biology · 2020Review
- The ties that bind: functional clusters in limb-girdle muscular dystrophy.Skeletal muscle · 2020Review
- Review
- Anti-Inflammatory and General Glucocorticoid Physiology in Skeletal Muscles Affected by Duchenne Muscular Dystrophy: Exploration of Steroid-Sparing Agents.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Muscular dystrophies are a group of genetic diseases that lead to muscle wasting and, in most cases, premature death. Cytokines and inflammatory factors are released during the disease process where they promote deleterious signaling events that directly participate in myofiber death. Here, we show that p38α, a kinase in the greater mitogen-activated protein kinase (MAPK)-signaling network, serves as a nodal regulator of disease signaling in dystrophic muscle. Deletion of Mapk14 (p38α-encoding gene) in the skeletal muscle of mdx- (lacking dystrophin) or sgcd- (δ-sarcoglycan-encoding gene) null mice resulted in a significant reduction in pathology up to 6 months of age. We also generated MAPK kinase 6 (MKK6) muscle-specific transgenic mice to model heightened p38α disease signaling that occurs in dystrophic muscle, which resulted in severe myofiber necrosis and many hallmarks of muscular dystrophy. Mechanistically, we show that p38α directly induces myofiber death through a mitochondrial-dependent pathway involving direct phosphorylation and activation of the pro-death Bcl-2 family member Bax. Indeed, muscle-specific deletion of Bax, but not the apoptosis regulatory gene Tp53 (encoding p53), significantly reduced dystrophic pathology in the muscles of MKK6 transgenic mice. Moreover, use of a p38 MAPK pharmacologic inhibitor reduced dystrophic disease in Sgcd(-/-) mice suggesting a future therapeutic approach to delay disease.
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Registered trials
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