HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling
HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling
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HuR 调节异丙肾上腺素诱导的心脏重塑中受磷蛋白的表达
DOI：
10.1093/cvr/cvz205
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发表时间：
2020-04-01
影响因子：
10.8
通讯作者：
Wang, Wengong
中科院分区：
文献类型：
--
作者：
Hu, Han;Jiang, Mingyang;Wang, Wengong
目的 在心力衰竭和心脏重塑中观察到受磷蛋白 (PLB) 表达升高，抑制 Ca2+ 泵与 Ca2+ 的亲和力，从而损害心脏舒张。然而，PLB 的调控机制仍有待进一步研究。本研究旨在检测RNA结合蛋白HuR在PLB调节中的作用以及该调节过程对心脏重塑的影响。方法与结果采用心肌细胞中特异性缺失HuR的小鼠模型来检测HuR在异丙肾上腺素（ISO）诱导的心脏重塑过程中调节PLB的作用。 HuR缺陷对静止状态下小鼠心脏的表型和功能没有显着影响。然而，心肌细胞中HuR的缺失减弱了ISO诱导PLB表达和减少β1-AR表达的作用，进而加剧ISO诱导的心肌肥大和心脏纤维化。在H9C2细胞中，HuR与PLB和β1-AR mRNA的结合分别稳定PLB mRNA和不稳定β1-AR mRNA。结论HuR稳定PLB mRNA并不稳定β1-AR mRNA。 HuR-PLB 和 HuR-β 1-AR 调节过程对 ISO 诱导的心脏重塑有影响。[图表]。
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].