# Inhibition of HuR/ELAVL-1 attenuates fibrotic progression in Mdx mice with dilated cardiomyopathy

## TL;DR

Inhibiting HuR reduces heart fibrosis and improves function in a mouse model of Duchenne muscular dystrophy-related heart disease.

## Contribution

This study identifies HuR as a novel therapeutic target for mitigating fibrotic progression in DCM associated with DMD.

## Key findings

- HuR is upregulated in cardiac tissues of mdx mice with DCM.
- Inhibition of HuR attenuates cardiac fibrosis and improves heart function in these mice.
- Targeting HuR shows potential for therapeutic intervention in DCM.

## Abstract

Duchenne muscular dystrophy (DMD) arises from dystrophin deficiency, a crucial component of the dystrophin-glycoprotein complex (DGC) essential for maintaining cellular structural integrity by linking intracellular actin filaments to the basal lamina. Dysfunctions within this complex, coupled with increased inflammatory immune cell infiltration, contribute to the onset of dilated cardiomyopathy (DCM). This cardiac condition, characterized by necrosis and fibrosis, significantly impairs left ventricular function. Despite various treatment approaches, reliable effects on these pathogenic mechanisms remain elusive. RNA-binding proteins play pivotal roles in modulating pathways often dysregulated in cardiac pathology. Notably, HuR, which is upregulated in fibrotic cardiac regions and modulates innate immune system activation, emerges as a promising target. We investigated HuR expression in cardiac tissues of mdx murine model of DMD and assessed the impact of its inhibition with regards to DCM progression. Our findings reveal that HuR is indeed upregulated in mdx mice, and its inhibition leads to attenuation of cardiac fibrosis and improvement in heart function. These preclinical results underscore the potential of targeting HuR for therapeutic intervention to mitigate DCM-associated pathological changes, warranting further exploration for the development of effective treatments.

The online version contains supplementary material available at 10.1007/s00018-025-05979-0.