ArticleHuman molecular genetics2015
Sarcospan integration into laminin-binding adhesion complexes that ameliorate muscular dystrophy requires utrophin and α7 integrin.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Aging reveals a sex-dependent susceptibility of sarcospan-deficient mice to cardiometabolic disease.American journal of physiology. Heart and circulatory physiology · 2024Article
- The Development of Robust Antibodies to Sarcospan, a Dystrophin- and Integrin-Associated Protein, for Basic and Translational Research.International journal of molecular sciences · 2024Article
- Sarcospan Deficiency Increases Oxidative Stress and Arrhythmias in Hearts after Acute Ischemia-Reperfusion Injury.International journal of molecular sciences · 2023Article
- Super-Resolution Imaging Reveals the Nanoscale Distributions of Dystroglycan and Integrin Itga7 in Zebrafish Muscle Fibers.Biomedicines · 2023Article
- Myoscaffolds reveal laminin scarring is detrimental for stem cell function while sarcospan induces compensatory fibrosis.NPJ Regenerative medicine · 2023Article
- The alpha7 integrin subunit in astrocytes promotes endothelial blood-brain barrier integrity.Development (Cambridge, England) · 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
- Promising therapeutic approaches of utrophin replacing dystrophin in the treatment of Duchenne muscular dystrophy.Fundamental research · 2022Review
- Proteomic Identification of Markers of Membrane Repair, Regeneration and Fibrosis in the Aged and Dystrophic Diaphragm.Life (Basel, Switzerland) · 2022Article
- Sarcospan increases laminin-binding capacity of α-dystroglycan to ameliorate DMD independent of Galgt2.Human molecular genetics · 2022Article
- Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies.Neuropathology and applied neurobiology · 2021Article
- Cellular pathology of the human heart in Duchenne muscular dystrophy (DMD): lessons learned from in vitro modeling.Pflugers Archiv : European journal of physiology · 2021Review
- Loss of sarcospan exacerbates pathology in mdx mice, but does not affect utrophin amelioration of disease.Human molecular genetics · 2021Article
- PDE10A Inhibition Reduces the Manifestation of Pathology in DMD Zebrafish and Represses the Genetic Modifier PITPNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Review
- High-throughput screening identifies modulators of sarcospan that stabilize muscle cells and exhibit activity in the mouse model of Duchenne muscular dystrophy.Skeletal muscle · 2020Article
- Development of a high-throughput screen to identify small molecule enhancers of sarcospan for the treatment of Duchenne muscular dystrophy.Skeletal muscle · 2019Article
- Laminin-111 protein therapy enhances muscle regeneration and repair in the GRMD dog model of Duchenne muscular dystrophy.Human molecular genetics · 2019Article
- Stabilization of the cardiac sarcolemma by sarcospan rescues DMD-associated cardiomyopathy.JCI insight · 2019Article
- Genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies.Muscle & nerve · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result in loss of the dystrophin-glycoprotein complex, a laminin receptor that connects the myofiber to its surrounding extracellular matrix. Utrophin, a dystrophin ortholog that is normally localized to the neuromuscular junction, is naturally upregulated in DMD muscle, which partially compensates for the loss of dystrophin. Transgenic overexpression of utrophin causes broad sarcolemma localization of utrophin, restoration of laminin binding and amelioration of disease in the mdx mouse model of DMD. We previously demonstrated that overexpression of sarcospan, a dystrophin- and utrophin-binding protein, ameliorates mdx muscular dystrophy. Sarcospan boosts levels of utrophin to therapeutic levels at the sarcolemma, where attachment to laminin is restored. However, understanding the compensatory mechanism is complicated by concomitant upregulation of α7β1 integrin, which also binds laminin. Similar to the effects of utrophin, transgenic overexpression of α7 integrin prevents DMD disease in mice and is accompanied by increased abundance of utrophin around the extra-synaptic sarcolemma. In order to investigate the mechanisms underlying sarcospan 'rescue' of muscular dystrophy, we created double-knockout mice to test the contributions of utrophin or α7 integrin. We show that sarcospan-mediated amelioration of muscular dystrophy in DMD mice is dependent on the presence of both utrophin and α7β1 integrin, even when they are individually expressed at therapeutic levels. Furthermore, we found that association of sarcospan into laminin-binding complexes is dependent on utrophin and α7β1 integrin.
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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 Socratic graph.