Autophagy decreases alveolar epithelial cell injury by regulating the release of inflammatory mediators. Issue 11 (21st January 2020)

• Record Type: Journal Article
• Authors: Fan, Tao; Yang, Shuo; Huang, Zhixin; Wang, Wei; Guo, Xiaobo; Pan, Shize; Zhang, Boyou; Xu, Yao; Fang, Yifan; Mao, Zhangfan; Hu, Hao; Geng, Qing
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 11(2020:Nov.)
• Page Start: 7982
• Page End: 7995
• Publication Date: 2020-01-21
• Subjects: alveolar epithelial cell -- autophagy -- hypoxia–reoxygenation (H/R) -- inflammation -- ischemia–reperfusion (I/R); Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29453
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in the 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‐MA) or an autophagy promoter (rapamycin), followed by hypoxia–reoxygenation treatment for 2, 4, and 6 hr in vitro. In vivo, 20 male Sprague Dawley rats were randomly divided into four groups (model group: No blocking of the hilum in the left lung; control group: Blocking of the hilum in the left lung for 1 hr with dimethyl sulfoxide lavage; 3‐MA group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of 3‐MA (5 μmol/L) solution lavage; and rapamycin group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of rapamycin (250 nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the nuclear factor kappa B signaling pathway and limited the expression of proinflammatory factors. A contrary result was found after the 3‐MA pretreatment. These findings indicate that autophagy reduces ischemia–reperfusion injury by repressing inflammatory signaling pathways in the early stages of hypoxia in vitro and in vivo. Autophagy could be a new protective method for application in lung ischemia–reperfusion injury. Abstract : Summary diagram that showing the classical autophagy signaling pathway and functional outcome of autophagy inhibition or promotion.