Mechanistic target of rapamycin-mediated autophagy is involved in the alleviation of lipopolysaccharide-induced acute lung injury in rats |
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| Institution: | 1. Institute of Traditional Chinese Medicine, Chinese PLA General Hospital, No. 28 Fuxin Road, Haidian district, Beijing 100853, People''s Republic of China;2. Institute of Radiation Medicine Sciences, Academy of Military Medical Sciences, No. 27 Taiping Road, Haidian district, Beijing 100850, People''s Republic of China;3. Institute of First Clinical Medical Colleges, Beijing University of Chinese Medicine, Beisanhuan east road, Chaoyang district, Beijing 100029, People''s Republic of China;1. Department of Anesthesiology, Critical Care and Pain Medicine, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, 109 Xueyuan Western Road, Wenzhou, Zhejiang Province 325027, PR China;2. Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, PR China;3. Department of Respiratory Medicine Tongde Hospital of Zhejiang Province, PR China;4. Department of Respiratory Medicine, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou 325027, PR China;1. Department of ICU, The First Hospital of Jilin University, Changchun 130021, PR China;2. Department of the First Operating Room, The First Hospital of Jilin University, Changchun 130021, PR China;3. Department of Radiology, The First Hospital of Jilin University, Changchun 130021, PR China;4. Department of the Second Operating Room, The First Hospital of Jilin University, Changchun 130021, PR China;5. Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130021, PR China;6. Department of Neonatology, The First Hospital of Jilin University, Changchun 130021, PR China |
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| Abstract: | Acute lung injury (ALI) is a complex clinical syndrome with high morbidity and mortality rates. Autophagy is an adaptive process that plays a complex role in ALI. The aim of this study was to investigate the effects of autophagy on lipopolysaccharide (LPS)-induced lung injury by establishing a rat ALI model and to further explore the possible mechanisms involved. Rats were pretreated with the autophagy inhibitor 3-methyladenine (3-MA) or the autophagy activator rapamycin before they were challenged with the intratracheal instillation of LPS (5 mg/kg). The level of autophagy in the lung tissue was detected. Lung injury and vascular permeability were assessed. The role of the mechanistic target of rapamycin (mTOR)-mediated Unc-51-like kinase 1 (ULK1) and the class III PI3 kinase VPS34 in autophagy regulation was examined. LPS challenge induced autophagy and rapamycin pretreatment enhanced autophagy activity in LPS-induced ALI rats. LPS caused severe lung injury and high pulmonary vascular permeability, which could be alleviated by enhancing autophagy. In addition, the inhibition of mTOR upregulated the expression of ULK1 and VPS34 and thus increased LPS-induced autophagy. Autophagy plays a protective role in LPS-induced ALI, and enhancing autophagy via the inhibition of mTOR alleviates lung injury and pulmonary barrier function. Moreover, mTOR negatively mediates ULK1 and VPS34 to regulate LPS-induced autophagy in rats. |
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| Keywords: | Acute lung injury Autophagy Lipopolysaccharide Mechanistic target of rapamycin 3-Methyladenine Rapamycin |
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