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Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway

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Abstract

Melatonin is well known for its cardioprotective effects; however, whether melatonin exerts therapeutic effects on cardiomyocyte hypertrophy remains to be investigated, as do the mechanisms underlying these effects, if they exist. Cyclophilin A (CyPA) and its corresponding receptor, CD147, which exists in a variety of cells, play crucial roles in modulating reactive oxygen species (ROS) production. In this study, we explored the role of the CyPA/CD147 signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and the protective effects exerted by melatonin against Ang II-induced injury in cultured H9C2 cells. Cyclosporine A, a specific CyPA/CD147 signaling pathway inhibitor, was used to manipulate CyPA/CD147 activity. H9C2 cells were then subjected to Ang II or CyPA treatment in either the absence or presence of melatonin. Our results indicate that Ang II induces cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway and promotes ROS production, which can be blocked by melatonin pretreatment in a concentration-dependent manner, in cultured H9C2 cells and that CyPA/CD147 signaling pathway inhibition protects against Ang II-induced cardiomyocyte hypertrophy. The protective effects of melatonin against Ang II-induced cardiomyocyte hypertrophy depend at least partially on CyPA/CD147 inhibition.

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Acknowledgments

The author(s) disclose receipt of the following financial support for this research and the authorship and/or publication of this article: funding support was provided by the National Natural Science Foundation of China (Nos. 81070076, 81170135), the National 973 Basic Research Program of China (No. 2012CB722406), and the Science Foundation of Qilu Hospital of Shandong (No. 2016QLQN17).

Author Contributions

This Project was conceived by Hongyan Su. The experiments were performed by Hongyan Su, Jingyuan Li, Tongshuai Chen, and Na Li. The results were interpreted by Hongyan Su, Jingyuan Li, Tongshuai Chen, Na Li, and Peili Bu. The manuscript was written and approved by all authors.

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Authors and Affiliations

  1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China

    Hongyan Su, Jingyuan Li, Tongshuai Chen, Na Li, Jie Xiao, Shujian Wang, Xiaobin Guo, Yi Yang & Peili Bu

  2. Department of Cardiology, Shandong Provincial Chest Hospital, 46 Lishan Road, Jinan, China

    Hongyan Su

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  1. Hongyan Su
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  2. Jingyuan Li
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Correspondence to Peili Bu.

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Su, H., Li, J., Chen, T. et al. Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway. Mol Cell Biochem 422, 85–95 (2016). https://doi.org/10.1007/s11010-016-2808-9

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