ArticleHuman molecular genetics2018
Downregulation of Survivin contributes to cell-cycle arrest during postnatal cardiac development in a severe spinal muscular atrophy mouse model.
Article in Human molecular genetics, 2018. 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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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- TLR2 mediates cell cycle re-entry and survival of neonatal cardiomyocytes in response to injury.Cell communication and signaling : CCS · 2026Article
- Multi-omics analysis of genetic drivers linking aortic stenosis and left ventricular diastolic dysfunction in heart failure.BioData mining · 2026Article
- SMN deficiency inhibits endochondral ossification via promoting TRAF6-induced ubiquitination degradation of YBX1 in spinal muscular atrophy.Bone research · 2025Article
- Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy.JCI insight · 2025Article
- New Perspectives of Underlying Cardiomyopathy in Pediatric SMA Patients-An Age Matched Control Study.Life (Basel, Switzerland) · 2025Article
- Transcriptional reprogramming in SMA mouse hearts reveals signatures of early heart failure and dysregulated calcium signaling.Human molecular genetics · 2025Article
- Whole-transcriptome sequencing in neural and non-neural tissues of a mouse model identifies miR-34a as a key regulator in SMA pathogenesis.Molecular therapy. Nucleic acids · 2025Article
- Repurposing Antiepileptic Drugs for Cancer: A Promising Therapeutic Strategy.Journal of clinical medicine · 2025Review
- Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA.Human molecular genetics · 2025Article
- [Molecular pathological mechanism of liver metabolic disorder in mice with severe spinal muscular atrophy].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Mitochondrial Dysfunction in Spinal Muscular Atrophy.International journal of molecular sciences · 2022Review
- Article
- Antisense Oligonucleotide Induction of the hnRNPA1b Isoform Affects Pre-mRNA Splicing ofInternational journal of molecular sciences · 2022Article
- Suppression of the necroptotic cell death pathways improves survival inFrontiers in cellular neuroscience · 2022Article
- History of development of the life-saving drug "Nusinersen" in spinal muscular atrophy.Frontiers in cellular neuroscience · 2022Review
- The alteration of left ventricular strain in later-onset spinal muscular atrophy children.Frontiers in cellular neuroscience · 2022Article
- Spinal Muscular Atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons.Acta neuropathologica communications · 2021Article
- Tart Cherry (Fruit ofMedicina (Kaunas, Lithuania) · 2021Article
- Troponin T amino acid mutation (ΔK210) knock-in mice as a neonatal dilated cardiomyopathy model.Pediatric research · 2021Article
- In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy.Brain sciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive degeneration of spinal-cord motor neurons, leading to atrophy of skeletal muscles. However, accumulating evidence indicates that it is a multi-system disorder, particularly in its severe forms. Several studies delineated structural and functional cardiac abnormalities in SMA patients and mouse models, yet the abnormalities have been primarily attributed to autonomic dysfunction. Here, we show in a severe mouse model that its cardiomyocytes undergo G0/G1 cell-cycle arrest and enhanced apoptosis during postnatal development. Microarray and real-time RT-PCR analyses revealed that a set of genes associated with cell cycle and apoptosis were dysregulated in newborn pups. Of particular interest, the Birc5 gene, which encodes Survivin, an essential protein for heart development, was down-regulated even on pre-symptomatic postnatal day 0. Interestingly, cultured cardiomyocytes depleted of SMN recapitulated the gene expression changes including downregulation of Survivin and abnormal cell-cycle progression; and overexpression of Survivin rescued the cell-cycle defect. Finally, increasing SMN in SMA mice with a therapeutic antisense oligonucleotide improved heart pathology and recovered expression of deregulated genes. Collectively, our data demonstrate that the cardiac malfunction of the severe SMA mouse model is mainly a cell-autonomous defect, caused by widespread gene deregulation in heart tissue, particularly of Birc5, resulting in developmental abnormalities through cell-cycle arrest and apoptosis.
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