ArticleHuman molecular genetics2009
Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 172 citations in OpenAlex.
- Temsirolimus safety evaluation: real-world adverse event analysis from the FDA adverse event reporting system database.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Nuclear envelope proteins in cancer: revisiting the significance of LEM-domain proteins.Frontiers in cell and developmental biology · 2026Review
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- Microtubule forces drive nuclear damage in LMNA cardiomyopathy.Nature cardiovascular research · 2025Article
- The dual guardians of cellular stability: exploring nesprin and lamin in senescence.Cell death & disease · 2025Review
- Deregulated nutrient response in ttntv cardiomyopathy can be repaired via Erk inhibition for cardioprotective effects.Journal of molecular and cellular cardiology · 2025Article
- Pervasive nuclear envelope ruptures precede ECM signaling and disease onset without activating cGAS-STING in Lamin-cardiomyopathy mice.Cell reports · 2024Article
- Global Proteomic Analysis Reveals Alterations in Differentially Expressed Proteins between Cardiopathic Lamin A/C Mutations.Journal of proteome research · 2024Article
- Perinuclear damage from nuclear envelope deterioration elicits stress responses that contribute toScience advances · 2024Article
- Pervasive nuclear envelope ruptures precede ECM signaling and disease onset without activating cGAS-STING in Lamin-cardiomyopathy mice.bioRxiv : the preprint server for biology · 2024Article
- From gene to mechanics: a comprehensive insight into the mechanobiology of LMNA mutations in cardiomyopathy.Cell communication and signaling : CCS · 2024Review
- A case report of a rare genetic mutation (LMNA-C.185G>C, p.Arg62Pro) associated with dilated cardiomyopathy in a Han Chinese child.Frontiers in cardiovascular medicine · 2024Article
- Emerin deficiency does not exacerbate cardiomyopathy in a murine model of Emery-Dreifuss muscular dystrophy caused by an LMNA gene mutation.The journal of physiological sciences : JPS · 2023Article
- Transcriptome studies of inherited dilated cardiomyopathies.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Targeting unfolded protein response reverts ER stress and ER CaJournal of translational medicine · 2023Article
- Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.Nature communications · 2022Article
- Preclinical Advances of Therapies for Laminopathies.Journal of clinical medicine · 2021Review
- The Role of Emerin in Cancer Progression and Metastasis.International journal of molecular sciences · 2021Review
- Article
- Ryanodine receptor remodeling in cardiomyopathy and muscular dystrophy caused by lamin A/C gene mutation.Human molecular genetics · 2021Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Autosomal Emery-Dreifuss muscular dystrophy and related disorders with dilated cardiomyopathy and variable skeletal muscle involvement are caused by mutations in LMNA, which encodes A-type nuclear lamins. How alterations in A-type lamins, intermediate filament proteins of the nuclear envelope expressed in most differentiated somatic cells, cause cardiomyopathy is only poorly understood. We demonstrated previously abnormal activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of Lmna H222P 'knock in' mice, a model of autosomal Emery-Dreifuss muscular dystrophy. We therefore treated Lmna(H222P/H222P) mice that develop cardiomyopathy with PD98059, an inhibitor of ERK activation. Systemic treatment of Lmna(H222P/H222P) mice with PD98059 inhibited ERK phosphorylation and blocked the activation of downstream genes in heart. It also blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in sarcomere organization that occurred in placebo-treated mice. Histological analysis and echocardiography demonstrated that treatment with PD98059 delayed the development of left ventricular dilatation. PD98059-treated Lmna(H222P/H222P) mice had normal cardiac ejection fractions assessed by echocardiography when placebo-treated mice had a 30% decrease. These results emphasize the role of ERK activation in the development of cardiomyopathy caused by LMNA mutations. They further provide proof of principle for ERK inhibition as a therapeutic option to prevent or delay heart failure in humans with Emery-Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA.
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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.