Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary arterial hypertension (PAH), pulmonary embolism (PE), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), obstructive sleep apnoea syndrome (OSAS), non-small cell lung cancer (NSCLC), pulmonary edema, asthma, and chronic obstructive pulmonary diseases. In detail, apelin/APJ system attenuates PAH by activating AMPK-KLF2-eNOS-NO signaling and miR424/503-FGF axis. Also, apelin protects against ALI/ARDS by reducing mitochondrial ROS-triggered oxidative damage, mitochondria apoptosis, and inflammatory responses induced by the activation of NF-κB and NLRP3 inflammasome. Apelin/APJ system also prevents the occurrence of pulmonary edema via activating AKT-NOS3-NO pathway. Moreover, apelin/APJ system accelerates NSCLC cells’ proliferation and migration via triggering ERK1/2–cyclin D1 and PAK1–cofilin signaling, respectively. Additionally, apelin/APJ system may act as a predictor in the development of OSAS and PE. Considering the pleiotropic actions of apelin/APJ system, targeting apelin/APJ system may be a potent therapeutic avenue for respiratory diseases.

Apelin是G蛋白偶联受体APJ的内源性配体。它在心脏，肝脏和肾脏等许多组织中广泛表达，尤其是在肺组织中。越来越多的证据表明，apelin / APJ系统与呼吸系统疾病的发展密切相关。因此，在本综述中，我们重点研究apelin / APJ系统在呼吸系统疾病中的作用，包括肺动脉高压（PAH），肺栓塞（PE），急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS），阻塞性睡眠呼吸暂停综合症（OSAS），非小细胞肺癌（NSCLC），肺水肿，哮喘和慢性阻塞性肺疾病。详细地说，apelin / APJ系统通过激活AMPK-KLF2-eNOS-NO信号传导和miR424 / 503-FGF轴来减弱PAH。也，apelin通过减少线粒体ROS触发的氧化损伤，线粒体凋亡以及由NF-κB和NLRP3炎性体激活引起的炎症反应，来预防ALI / ARDS。Apelin / APJ系统还可以通过激活AKT-NOS3-NO途径来防止肺水肿的发生。此外，apelin / APJ系统分别通过触发ERK1 / 2–cyclin D1和PAK1–cofilin信号传导来加速NSCLC细胞的增殖和迁移。另外，apelin / APJ系统可能在OSAS和PE的发展中起预测作用。考虑到apelin / APJ系统的多效作用，靶向apelin / APJ系统可能是呼吸道疾病的有效治疗途径。Apelin / APJ系统还可以通过激活AKT-NOS3-NO途径来防止肺水肿的发生。此外，apelin / APJ系统分别通过触发ERK1 / 2–cyclin D1和PAK1–cofilin信号传导来加速NSCLC细胞的增殖和迁移。另外，apelin / APJ系统可能在OSAS和PE的发展中起预测作用。考虑到apelin / APJ系统的多效作用，靶向apelin / APJ系统可能是呼吸道疾病的有效治疗途径。Apelin / APJ系统还可以通过激活AKT-NOS3-NO途径来防止肺水肿的发生。此外，apelin / APJ系统分别通过触发ERK1 / 2–cyclin D1和PAK1–cofilin信号传导来加速NSCLC细胞的增殖和迁移。另外，apelin / APJ系统可能在OSAS和PE的发展中起预测作用。考虑到apelin / APJ系统的多效作用，靶向apelin / APJ系统可能是呼吸道疾病的有效治疗途径。