HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling.

The elevated expression of phospholamban (PLB) has been observed in heart failure and cardiac remodelling, inhibiting the affinity of Ca2+ pump to Ca2+ thereby impairing heart relaxation. However, the mechanisms underlying the regulation of PLB remains to be further studied. The present study aims to test the role of RNA-binding protein HuR in the regulation of PLB and the impact of this regulatory process in cardiac remodelling. A mouse model specifically deleted HuR in cardiomyocytes were used for testing the role of HuR in regulating PLB during isoproterenol (ISO)-induced cardiac remodelling. HuR deficiency did not significantly influence the phenotype and function of mouse heart under static status. However, deletion of HuR in cardiomyocytes mitigated the effect of ISO in inducing PLB expression and reducing β1-AR expression, in turn aggravating ISO-induced myocardial hypertrophy and cardiac fibrosis. In H9C2 cells, association of HuR with PLB and β1-AR mRNAs stabilized PLB mRNA and destabilized β1-AR mRNA, respectively. HuR stabilizes PLB mRNA and destabilizes β1-AR mRNA. The HuR-PLB and HuR-β1-AR regulatory processes impact on ISO-induced cardiac remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.

Citation

Han Hu, Mingyang Jiang, Yangpo Cao, Zhuojun Zhang, Bin Jiang, Feng Tian, Juan Feng, Yali Dou, Myriam Gorospe, Ming Zheng, Lemin Zheng, Zhongzhou Yang, Wengong Wang. HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling. Cardiovascular research. 2020 Apr 01;116(5):944-955

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PMID: 31373621

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