• Hongshu Sui, Mingjiu Luo, Yaya Miao, Wanjing Cheng, Shan Wen, Bohou Zhao, Yuming Li, Zengyun Qiao, Yaling Liu, and Changlong Xu.
• Department of Histology and Embryology, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong 271000, PR China.
• Respir Physiol Neurobiol. 2020 Feb 1; 273: 103338.

ObjectiveThe beneficial role of Cystic fibrosis transmembrane conductance regulator (CFTR) was reported in acute lung injury (ALI), however, there was no direct evidence supporting the relationship between CFTR and cell autophagy in ALI. Here, this study is to analyze the protective role of CFTR on autophagy in lipopolysaccharide (LPS)-induced ALI mice and its special mechanism.MethodsALI mouse models were established by the stimulation of LPS. ALI mice were subjected to tail vein injection of Lv-CFTR, intraperitoneal injection of autophagy activator RAPA or tail vein injection of Lv-sh-HMGB1 before lung tissues and bronchoalveolar lavage fluid (BALF) were collected. The expression levels of CFTR, HMGB1, Beclin-1, p62, p-AKT, p-mTOR, and LC3-II/LC3-I ratio were estimated by qRT-PCR and Western blot. The lung edema in ALI mice was inspected by wet/dry weight (W/D) ratio. Hematoxylin and eosin (H&E) staining was utilized to observe pathological features of lung tissue. Immunofluorescence was applied to determine the expression intensity of LC-3. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were assayed, and inflammatory response in ALI mice was measured.ResultsALI mouse models were successfully induced by LPS, evidenced by an enhanced inflammatory response in lung tissues, heightened W/D ratio and cell autophagy markers. ALI mice had suppressed expression of CFTR, while injection of CFTR overexpression in ALI mice attenuated inflammation, autophagy, MPO activity and MDA content in addition to elevating SOD activity. Moreover, CFTR overexpression could increase the p-AKT, and p-mTOR. Overexpression of HMGB1 could reverse the expression pattern in mice injected with CFTR overexpression.ConclusionCFTR could inhibit cell autophagy by enhancing PI3K/AKT/mTOR signaling pathway, thereby playing a protective role in LPS-induced ALI in mice.Copyright © 2019 Elsevier B.V. All rights reserved.

28 keywords...

hide…