Toxicology and Biomedicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam.
College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.
J Cell Physiol. 2018 Nov;233(11):8458-8466. doi: 10.1002/jcp.26790. Epub 2018 Jun 1.
Heart failure (HF) remains a major cause of morbidity and mortality worldwide. The primary cause identified for HF is impaired left ventricular myocardial function, and clinical manifestations may lead to severe conditions like pulmonary congestion, splanchnic congestion, and peripheral edema. Development of new therapeutic strategies remains the need of the hour for controlling the problem of HF worldwide. Deeper insights into the molecular mechanisms involved in etiopathology of HF indicate the significant role of calcium signaling, autocrine signaling pathways, and insulin-like growth factor-1 signaling that regulates the physiologic functions of heart growth and development such as contraction, metabolism, hypertrophy, cytokine signaling, and apoptosis. In view of these facts, a transcription factor (TF) regulating the myriad of these signaling pathways may prove as a lead candidate for development of therapeutics. Adenovirus E4 promoter-binding protein (E4BP4), also known as nuclear-factor, interleukin 3 regulated (NFIL3), a type of basic leucine zipper TF, is known to regulate the signaling processes involved in the functioning of heart. The current review discusses about the expression, structure, and functional role of E4BP4 in signaling processes with emphasis on calcium signaling mechanisms, autocrine signaling, and insulin-like growth factor II receptor-mediated processes regulated by E4BP4 that may regulate the pathogenesis of HF. We propose that E4BP4, being the critical component for the regulation of the above signaling processes, may serve as a novel therapeutic target for HF, and scientific investigations are merited in this direction.
心力衰竭（HF）仍然是全世界发病率和死亡率的主要原因。HF 的主要病因是左心室心肌功能受损，临床表现可能导致严重的肺部充血、内脏充血和外周水肿等情况。开发新的治疗策略仍然是控制全球 HF 问题的当务之急。对 HF 病因发病机制中涉及的分子机制的更深入了解表明，钙信号、自分泌信号通路和胰岛素样生长因子-1 信号通路在调节心脏生长和发育的生理功能方面（如收缩、代谢、肥大、细胞因子信号和细胞凋亡）起着重要作用。鉴于这些事实，一种调节这些信号通路的转录因子（TF）可能被证明是开发治疗方法的候选药物。腺病毒 E4 启动子结合蛋白（E4BP4），也称为核因子、白细胞介素 3 调节（NFIL3），是一种碱性亮氨酸拉链 TF，已知可调节与心脏功能相关的信号转导过程。目前的综述讨论了 E4BP4 在信号转导过程中的表达、结构和功能作用，重点讨论了钙信号机制、自分泌信号以及 E4BP4 调节的胰岛素样生长因子 II 受体介导的过程，这些过程可能调节 HF 的发病机制。我们提出，E4BP4 作为调节上述信号转导过程的关键组成部分，可能成为 HF 的一个新的治疗靶点，值得在这方面进行科学研究。
