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Apelin/APJ system: an emerging therapeutic target for respiratory diseases

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Abstract

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.

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Acknowledgements

The study was supported by Grants from the National Natural Science Foundation of China (81603108) and Hunan Provincial Natural Science Foundation (2019JJ80063).

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  1. Jialong Yan and Aiping Wang have contributed equally to this work.

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  1. Institute of Clinical Research, Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, Hunan, People’s Republic of China

    Aiping Wang & Jiangang Cao

  2. Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, People’s Republic of China

    Jialong Yan & Linxi Chen

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Yan, J., Wang, A., Cao, J. et al. Apelin/APJ system: an emerging therapeutic target for respiratory diseases. Cell. Mol. Life Sci. 77, 2919–2930 (2020). https://doi.org/10.1007/s00018-020-03461-7

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