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Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators

Tao Fan, Shuo Yang, Zhixin Huang, Wei Wang, Shize Pan, Yao Xu, Boyou Zhang, Zhangfan Mao, Yifan Fang, Xiaobo Guo, Hao Hu, Qing Geng
doi: https://doi.org/10.1101/328039
Tao Fan
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Shuo Yang
Department of Cardiology, Renmin Hospital, Wuhan University, Cardiovascular 10 Research Institute of Wuhan University, 238th Jiefang Road, Wuhan, 430060, China
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Zhixin Huang
Department of Gynecology and Obstetrics, Renmin Hospital, Wuhan University, 12 238th Jiefang Road, Wuhan 430060, China
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Wei Wang
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Shize Pan
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Yao Xu
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Boyou Zhang
Department of Emergency, Beijing Ji Shui Tan Hospital, 31 Xinjiekou East Street, 14 Xicheng District, Beijing, 100035, China
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Zhangfan Mao
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Yifan Fang
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Xiaobo Guo
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Hao Hu
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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Qing Geng
Department of Thoracic Surgery, Renmin Hospital, Wuhan University, 238th Jiefang 8 Road, Wuhan 430060, China
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  • For correspondence: szgqing@126.com
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Abstract

To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment at 2, 4 and 6h in vitro. In vivo, twenty-four male Sprague-Dawley rats were randomly divided into four groups (model group: no blocking of hilum in the left lung; control group: blocking of hilum in the left lung for 1h with DMSO lavage; 3-MA group: blocking of hilum in the left lung for 1h with 100ml/kg of 3-MA (5μmol/L) solution lavage; rapamycin group: blocking of hilum in the left lung for 1h with 100ml/kg of rapamycin (250nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the NF-κB signaling pathway, restrained the expression of pro-inflammatory factors. A contrary result was confirmed by 3-MA pretreatment. These findings indicate that autophagy reduces ischemia-reperfusion injury by repressing inflammatory signaling pathways in the early stage of hypoxia in vitro and in vivo. This could be a new protective method for lung ischemia-reperfusion injury.

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Posted May 22, 2018.
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Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators
Tao Fan, Shuo Yang, Zhixin Huang, Wei Wang, Shize Pan, Yao Xu, Boyou Zhang, Zhangfan Mao, Yifan Fang, Xiaobo Guo, Hao Hu, Qing Geng
bioRxiv 328039; doi: https://doi.org/10.1101/328039
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Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators
Tao Fan, Shuo Yang, Zhixin Huang, Wei Wang, Shize Pan, Yao Xu, Boyou Zhang, Zhangfan Mao, Yifan Fang, Xiaobo Guo, Hao Hu, Qing Geng
bioRxiv 328039; doi: https://doi.org/10.1101/328039

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