The function of zfp91 is mainly studied in vitro, but there is no study in vivo. Accumulative data suggest that zfp91 may be an important gene to regulate all aspects of human response. However, there are no data to date about the function of zfp91 on cardiac homeostasis. Thus, we aimed to observe the role of zfp91 gene in mouse cardiomyocytes on myocardial homeostasis and related mechanisms under pressure overload. In the study, zfp91 mRNA and protein levels were significantly reduced in TAC‐operated WT mice as compared with controls. Genetic ablation of zfp91 dramatically led to pathological cardiac dysfunction and hypertrophy after transverse aortic constriction (TAC). Adenosine A1 receptor (Adora1) mRNA and protein expressions were significantly down‐regulated in the heart of zfp91‐deletion mice with TAC. Zfp91 overexpression reversed isoproterenol‐induced cardiomyocyte hypertrophy, which was abolished by selective Adora1 antagonist. Dual‐luciferase reporter and ChIP‐qPCR assays indicated that zfp91 acted on Adora1 promoter through its binding site. Last, Adora1 agonist rescued heart dysfunction and cardiac hypertrophy in zfp91 loss mice after TAC. Zfp91 may transcriptionally regulate Adora1 expression in the heart, which mainly maintained cardiac homeostasis under pressure overload status. It will provide a new approach to treat cardiac hypertrophy.

中文翻译：

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锌指蛋白91缺失通过在压力超负荷状态下腺苷A1受体下调引起心肌肥大。

zfp91的功能主要在体外研究，但没有体内研究。累积数据表明zfp91可能是调控人类反应各个方面的重要基因。但是，迄今为止，尚无有关zfp91对心脏动态平衡功能的数据。因此，我们旨在观察zfp91基因在小鼠心肌细胞在压力超负荷下对心肌动态平衡的作用及相关机制。在这项研究中，与对照组相比，在TAC操纵的WT小鼠中zfp91 mRNA和蛋白水平显着降低。zfp91的遗传消融横断性主动脉缩窄（TAC）后严重导致病理性心脏功能障碍和肥大。在患有TAC的zfp91缺失小鼠的心脏中，腺苷A1受体（Adora1）mRNA和蛋白表达显着下调。Zfp91的过表达逆转了异丙肾上腺素诱导的心肌肥大，选择性Adora1拮抗剂消除了这种肥大。双荧光素酶报告基因和ChIP-qPCR分析表明zfp91通过其结合位点作用于Adora1启动子。最后，Adora1激动剂挽救了z fp91的心脏功能障碍和心脏肥大TAC后丢失的小鼠。Zfp91可能通过转录调节心脏中的Adora1表达，而后者在压力超负荷状态下主要维持心脏稳态。它将提供一种治疗心脏肥大的新方法。