Journal
CARDIOVASCULAR RESEARCH
Volume 116, Issue 5, Pages 944-955Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvz205
Keywords
HuR; PLB; beta 1-AR; mRNA turnover; Cardiac remodelling
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Funding
- National Key Research and Development Program of China [2017YFA0504302]
- National Natural Science Foundation of China [81420108016, 81741003, 91749208]
- NIA IRP
- NIH
- NATIONAL INSTITUTE ON AGING [ZIAAG000394, ZIAAG000511] Funding Source: NIH RePORTER
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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 beta 1-AR expression, in turn aggravating ISO-induced myocardial hypertrophy and cardiac fibrosis. In H9C2 cells, association of HuR with PLB and beta 1-AR mRNAs stabilized PLB mRNA and destabilized beta 1-AR mRNA, respectively. Conclusion HuR stabilizes PLB mRNA and destabilizes beta 1-AR mRNA. The HuR-PLB and HuR-beta 1-AR regulatory processes impact on ISO-induced cardiac remodelling. [GRAPHICS] .
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