ArticleHuman molecular genetics2014
Caspase-12 ablation preserves muscle function in the mdx mouse.
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 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Long-term imoxin treatment does not attenuate disease severity in dystrophic diaphragm of male mice.Physiological reports · 2026Article
- The Age-Dependent Resident Myonuclear Multi-Omic Response to an Acute Skeletal Muscle Hypertrophic Stimulus in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Age-related transcriptional drift and physiological adaptation in long-living Ames dwarf skeletal muscle.NAR molecular medicine · 2026Article
- Autophagy selectively clears ER in TNF-α-induced muscle atrophy.Autophagy reports · 2026Article
- New Role of Protein Misfolding Corrector in the ER Stress-Inflammation Axis: Possible Therapeutic Indication in Neuronal and Epithelial Tumor Cells.International journal of molecular sciences · 2025Article
- The Age-Dependent Resident Myonuclear Multi-Omic Response to a Skeletal Muscle Hypertrophic Stimulus.bioRxiv : the preprint server for biology · 2025Article
- Three decades of caspases and RIPKs in life and death.Human molecular genetics · 2025Review
- Exploring caspase functions in mouse models.Apoptosis : an international journal on programmed cell death · 2024Review
- Loss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Ablation of specific insulin-like growth factor I forms reveals the importance of cleavage for regenerative capacity and glycosylation for skeletal muscle storage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Atrogin-1 promotes muscle homeostasis by regulating levels of endoplasmic reticulum chaperone BiP.JCI insight · 2024Article
- Cilostazol attenuates oxidative stress and apoptosis in the quadriceps muscle of the dystrophic mouse experimental model.International journal of experimental pathology · 2023Article
- Transplantation of Differentiated Tonsil-Derived Mesenchymal Stem Cells Ameliorates Murine Duchenne Muscular Dystrophy via Autophagy Activation.Tissue engineering and regenerative medicine · 2022Article
- Confounding Roles of ER Stress and the Unfolded Protein Response in Skeletal Muscle Atrophy.International journal of molecular sciences · 2021Review
- Cellular Stress in the Pathogenesis of Muscular Disorders-From Cause to Consequence.International journal of molecular sciences · 2020Review
- CACNA1H downregulation induces skeletal muscle atrophy involving endoplasmic reticulum stress activation and autophagy flux blockade.Cell death & disease · 2020Article
- ER stress in skeletal muscle remodeling and myopathies.The FEBS journal · 2019Review
- Molecular Insights into Muscle Homeostasis, Atrophy and Wasting.Current genomics · 2018Review
- Exciting perspectives for Translational Myology in the Abstracts of the 2018Spring PaduaMuscleDays: Giovanni Salviati Memorial - Chapter II - Abstracts of March 15, 2018.European journal of translational myology · 2018Article
- Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease.Journal of cellular physiology · 2018Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin. Several downstream consequences of dystrophin deficiency are triggers of endoplasmic reticulum (ER) stress, including loss of calcium homeostasis, hypoxia and oxidative stress. During ER stress, misfolded proteins accumulate in the ER lumen and the unfolded protein response (UPR) is triggered, leading to adaptation or apoptosis. We hypothesized that ER stress is heightened in dystrophic muscles and contributes to the pathology of DMD. We observed increases in the ER stress markers BiP and cleaved caspase-4 in DMD patient biopsies, compared with controls, and an increase in multiple UPR pathways in muscles of the dystrophin-deficient mdx mouse. We then crossed mdx mice with mice null for caspase-12, the murine equivalent of human caspase-4, which are resistant to ER stress. We found that deleting caspase-12 preserved mdx muscle function, resulting in a 75% recovery of both specific force generation and resistance to eccentric contractions. The compensatory hypertrophy normally found in mdx muscles was normalized in the absence of caspase-12; this was found to be due to decreased fibre sizes, and not to a fibre type shift or a decrease in fibrosis. Fibre central nucleation was not significantly altered in the absence of caspase-12, but muscle fibre degeneration found in the mdx mouse was reduced almost to wild-type levels. In conclusion, we have identified heightened ER stress and abnormal UPR signalling as novel contributors to the dystrophic phenotype. Caspase-4 is therefore a potential therapeutic target for DMD.
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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.