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Angiotensin II-Induced Early and Late Inflammatory Responses Through NOXs and MAPK Pathways

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Abstract

Angiotensin II (Ang II) dysregulation has been determined as cause or an effect of many diseases. The relationship between Ang II and reactive oxygen species (ROS), which are generated by enzymes in the nicotinamide adenine dinucleotide phosphate oxidase (NOX) family, has been the focus of many researchers for years. Inflammation in response to the activities of various NOXs with differing time-dependent characteristics was reported. It is still unclear how these factors interplay over the course of the inflammatory response and how signal transduction through mitogen-activated protein kinase (MAPK) pathways. Our study collected data on the effects of Ang II on human umbilical vascular endothelial cells (HUVECs) over a comprehensive time period. Our results demonstrated that NOXs had two time-dependent reactions in response to Ang II stimulation via MAPK pathways. First, ROS was produced only during the early inflammatory phase. NOX4 promoted more rapid generation of H2O2 via the JNK pathway than generation of O2·− via ERK1/2 and p38 pathways. During both the early and late phases of the inflammatory response, NOX4 activity was transduced through the JNK pathway, whereas NOX1 and NOX2 signals were transmitted via the ERK1/2 and p38 pathways. Signal transduction via ROS generation was more likely during the early phase of the inflammatory response, and increased cytokine levels were more likely induced by the late phase of the inflammatory response.

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Acknowledgments

We give our sincere thanks to Lixue Chen, Weixue Tang, Jingmei Xie, Yao Xiao, Xiaojuan Deng, and Guangchen Qin at the central laboratory of the First Affiliated Hospital of Chongqing Medical University for their assistance while we conducted our experiments.

Author Contributions

X. Zhang conceived the study and designed the experiments. X. Zhang, J. Yang and X.Y. Yu performed all of the experiments. X. Zhang analyzed the data and wrote the manuscript. S. Cheng assisted in editing the figures. H. Gan and Y.F. Xia reviewed and revised the paper.

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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

    Xi Zhang, Jia Yang, Xinyi Yu, Hua Gan & Yunfeng Xia

  2. Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Si Cheng

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  1. Xi Zhang
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Correspondence to Hua Gan.

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Zhang, X., Yang, J., Yu, X. et al. Angiotensin II-Induced Early and Late Inflammatory Responses Through NOXs and MAPK Pathways. Inflammation 40, 154–165 (2017). https://doi.org/10.1007/s10753-016-0464-6

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  • DOI: https://doi.org/10.1007/s10753-016-0464-6

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