ArticleHuman molecular genetics2016
Genetic overexpression of Serpina3n attenuates muscular dystrophy in mice.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Skeletal muscle methylome-transcriptome disruptions during the onset and progression of colorectal cancer-induced cachexia.American journal of physiology. Cell physiology · 2026Article
- Direct aldosterone stimulation of skeletal muscle fibroblasts changes gene expression and differentially affects fibroblast functions from normal and diseased muscles.Frontiers in physiology · 2026Article
- Oncostatin M signaling drives cancer-associated skeletal muscle wasting.Cell reports. Medicine · 2024Article
- The transcriptional regulator KLF15 is necessary for myoblast differentiation and muscle regeneration by activating FKBP5.The Journal of biological chemistry · 2023Article
- Skeletal muscle omics signatures in cancer cachexia: perspectives and opportunities.Journal of the National Cancer Institute. Monographs · 2023Article
- An ancient testis-specific IQ motif-containing H gene regulates specific transcript isoform expression during spermatogenesis.Development (Cambridge, England) · 2023Article
- SerpinA3N deficiency attenuates steatosis and enhances insulin signaling in male mice.The Journal of endocrinology · 2023Article
- Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Multi-omics analysis of sarcospan overexpression in mdx skeletal muscle reveals compensatory remodeling of cytoskeleton-matrix interactions that promote mechanotransduction pathways.Skeletal muscle · 2023Article
- Skeletal Muscle Regeneration in Cardiotoxin-Induced Muscle Injury Models.International journal of molecular sciences · 2022Review
- Microglia shield the murine brain from damage mediated by the cytokines IL-6 and IFN-α.Frontiers in immunology · 2022Article
- A network of core and subtype-specific gene expression programs in myositis.Acta neuropathologica · 2021Article
- Serpinb1a suppresses osteoclast formation.Biochemistry and biophysics reports · 2021Article
- A Potential Role for SerpinA3N in Acetaminophen-Induced Hepatotoxicity.Molecular pharmacology · 2021Article
- Muscle NADMolecular metabolism · 2020Article
- Marked Increased Production of Acute Phase Reactants by Skeletal Muscle during Cancer Cachexia.Cancers · 2020Article
- Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.Journal of cachexia, sarcopenia and muscle · 2020Article
- SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury.Cell death discovery · 2020Article
- Increased Serpina3n release into circulation during glucocorticoid-mediated muscle atrophy.Journal of cachexia, sarcopenia and muscle · 2018Article
- Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and Remodeling.Circulation research · 2018Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Muscular dystrophy (MD) is associated with mutations in genes that stabilize the myofiber plasma membrane, such as through the dystrophin-glycoprotein complex (DGC). Instability of this complex or defects in membrane repair/integrity leads to calcium influx and myofiber necrosis leading to progressive dystrophic disease. MD pathogenesis is also associated with increased skeletal muscle protease levels and activity that could augment weakening of the sarcolemma through greater degradation of cellular attachment complexes. Here, we observed a compensatory increase in the serine protease inhibitor Serpina3n in mouse models of MD and after acute muscle tissue injury. Serpina3n muscle-specific transgenic mice were generated to model this increase in expression, which reduced the activity of select proteases in dystrophic skeletal muscle and protected muscle from both acute injury with cardiotoxin and from chronic muscle disease in the mdx or Sgcd(-/-) MD genetic backgrounds. The Serpina3n transgene mitigated muscle degeneration and fibrosis, reduced creatine kinase serum levels, restored running capacity on a treadmill and reduced muscle membrane leakiness in vivo that is characteristic of mdx and Sgcd(-/-) mice. Mechanistically, we show that increased Serpina3n promotes greater sarcolemma membrane integrity and stability in dystrophic mouse models in association with increased membrane residence of the integrins, the DGC/utrophin-glycoprotein complex of proteins and annexin A1. Hence, Serpina3n blocks endogenous increases in the activity of select skeletal muscle resident proteases during injury or dystrophic disease, which stabilizes the sarcolemma leading to less myofiber degeneration and increased regeneration. These results suggest the use of select protease inhibitors as a strategy for treating MD.
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