Heart failure & cardiomyopathies
Deficiency of the RNA-binding protein RBMS1 improves myocardial fibrosis and heart failure
Authors' conclusion
These findings unveil a critical role of RBMS1 in regulating cardiac fibrosis through controlling the splicing of LMO7 to activate the TGF-β1 pathway. Genetic ablation or pharmacological inhibition of RBMS1 improves cardiac function in mice
Study context
- Population
- Heart failure (HF) patients and mice (MI model); human cardiac fibroblasts
Methodological detailsfibroblast-specific knockout mice, human and murine hearts
- Fibroblast-specific knockout mice
- Human and murine hearts
Main finding
As reported in the abstract
- RBMS1 expression increased in murine hearts after MI and in hearts of patients with ischaemic and hypertrophic cardiomyopathy
- RBMS1 levels in hearts of HF patients positively associated with cardiac fibrosis
- Fibroblast-specific ablation of RBMS1 improved cardiac dysfunction by mitigating myocardial fibrosis
- RBMS1 regulated alternative splicing (AS) of LMO7 (binding intron 19, splicing out exon 20) forming LMO7-Δe20, which activated the transforming growth factor (TGF)-β1 pathway by upregulating activator protein 1
- LMO7-Δe20 overexpression in mice caused cardiac fibrosis and dysfunction, ablated by TGF-β1 pathway inhibitor SB431542
- SB431542 attenuated RBMS1-driven fibrogenesis in human cardiac fibroblasts
- Low-dose nortriptyline or antisense oligonucleotide-mediated RBMS1 deficiency alleviated myocardial fibrosis and improved cardiac function in HF mice
Original publication
Deficiency of the RNA-binding protein RBMS1 improves myocardial fibrosis and heart failure. Eur Heart J. Published 5 June 2025. doi:10.
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