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HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling.


ABSTRACT:

Aims

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.

Methods and results

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 ?1-AR expression, in turn aggravating ISO-induced myocardial hypertrophy and cardiac fibrosis. In H9C2 cells, association of HuR with PLB and ?1-AR mRNAs stabilized PLB mRNA and destabilized ?1-AR mRNA, respectively.

Conclusion

HuR stabilizes PLB mRNA and destabilizes ?1-AR mRNA. The HuR-PLB and HuR-?1-AR regulatory processes impact on ISO-induced cardiac remodelling.

SUBMITTER: Hu H 

PROVIDER: S-EPMC7868665 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling.

Hu Han H   Jiang Mingyang M   Cao Yangpo Y   Zhang Zhuojun Z   Jiang Bin B   Tian Feng F   Feng Juan J   Dou Yali Y   Gorospe Myriam M   Zheng Ming M   Zheng Lemin L   Yang Zhongzhou Z   Wang Wengong W  

Cardiovascular research 20200401 5


<h4>Aims</h4>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.<h4>Methods and results</h4>A mouse model specifically  ...[more]

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