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CX3CL1/CX3CR1 Axis Contributes to Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation and Inflammatory Cytokine Production

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Abstract

Angiotensin II (Ang II) dysregulation has been determined in many diseases. The CX3CL1/CX3CR1 axis, which has a key role in cardiovascular diseases, is involved in the proliferation and inflammatory cytokine production of vascular smooth muscle cells (VSMCs). In this study, we aim to explore whether Ang II has a role in the expression of CX3CL1/CX3CR1, thus contributing to the proliferation and pro-inflammatory status of VSMCs. Cultured mouse aortic VSMCs were stimulated with 100 nmol/L of Ang II, and the expression of CX3CR1 was assessed by western blot. The results demonstrated that Ang II significantly up-regulated CX3CR1 expression in VSMCs and induced the production of reactive oxygen species (ROS) and the phosphorylation of p38 MAPK. Inhibitors of NADPH oxidase, ROS, and AT1 receptor significantly reduced Ang II-induced CX3CR1 expression. Targeted disruption of CX3CR1 by transfection with siRNA significantly attenuated Ang II-induced VSMC proliferation as well as down-regulated the expression of proliferating cell nuclear antigen (PCNA). Furthermore, CX3CR1-siRNA suppressed the effect of Ang II on stimulating Akt phosphorylation. Besides, the use of CX3CR1-siRNA decreased inflammatory cytokine production induced by Ang II treatment. Our results indicate that Ang II up-regulates CX3CR1 expression in VSMCs via NADPH oxidase/ROS/p38 MAPK pathway and that CX3CL1/CX3CR1 axis contributes to the proliferative and pro-inflammatory effects of Ang II in VSMCs.

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Acknowledgments

We sincerely thank Lixue Chen, Wenhui Yan, and Xiaojuan Deng at the central laboratory of the First Affiliated Hospital of Chongqing Medical University for their technical assistance while we conducted our experiments.

Funding

This study was funded by Wu Jieping Medical Foundation (No. 320.6750.16196) and the Medical Research and Developmental Fund of the First Affiliated Hospital of Chongqing Medical University (No. PYJJ2017-02).

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Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Chengsheng Li, Jin He, Xiaoyi Zhong, Hua Gan & Yunfeng Xia

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  1. Chengsheng Li
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  2. Jin He
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  3. Xiaoyi Zhong
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  4. Hua Gan
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  5. Yunfeng Xia
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Contributions

Chengsheng Li and Yunfeng Xia conceived the study and designed the experiments. Chengsheng Li, Jin He, and Xiaoyi Zhong performed all of the experiments. Chengsheng Li analyzed the data and wrote the manuscript. Hua Gan and Yunfeng Xia reviewed and revised the paper.

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Correspondence to Yunfeng Xia.

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Li, C., He, J., Zhong, X. et al. CX3CL1/CX3CR1 Axis Contributes to Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation and Inflammatory Cytokine Production. Inflammation 41, 824–834 (2018). https://doi.org/10.1007/s10753-018-0736-4

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  • DOI: https://doi.org/10.1007/s10753-018-0736-4

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