Fibroblast-Specific Depletion of Human Antigen R Alleviates Myocardial Fibrosis Induced by Cardiac Stress.

Cardiac fibrosis can be mitigated by limiting fibroblast-to-myofibroblast differentiation and proliferation. Human antigen R (HuR) modulates messenger RNA stability and expression of multiple genes. However, the direct role of cardiac myofibroblast HuR is unknown. Myofibroblast-specific deletion of HuR limited cardiac fibrosis and preserved cardiac functions in pressure overload injury. Knockdown of HuR in transforming growth factor-β1-treated cardiac fibroblasts suppressed myofibroblast differentiation and proliferation. HuR deletion abrogated the expression and messenger RNA stability of cyclins D1 and A2, suggesting a potential mechanism by which HuR promotes myofibroblast proliferation. Overall, these data suggest that inhibition of HuR could be a potential therapeutic approach to limit cardiac fibrosis.
Competing Interests: This work was supported by National Institutes of Health grants HL116729 (Dr Krishnamurthy) and HL138023 (Drs Krishnamurthy and Zhang), an American Heart Association Transformational Project Award (19TPA34850100, Dr Krishnamurthy), and an American Heart Association postdoctoral fellowship (916497, Dr Singh). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2024 The Authors.)