caa a22 4500 606235191 CHVBK 20210128101241.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2494-z doi (NATIONALLICENCE)springer-10.1007/s11010-015-2494-z Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells [Elektronische Daten] [Liang Zhang, Shuang Zhao, Li-Jie Yuan, Hong-Min Wu, Hong Jiang, Shi-Meng Zhao, Gang Luo, Xin-Dong Xue] Surfactant protein C (SP-C) deficiency is a risk factor for hyperoxia-induced bronchopulmonary dysplasia in newborn infants. However, the role of SP-C deficiency in the process is unclear. Here, using neonatal rat BPD model and MLE-12, mouse alveolar epithelial type II cell, we examined the changes of SP-C levels during hyperoxia. Immunohistochemistry, immunofluorescence, and ELISA analysis showed SP-C accumulation in alveolar epithelial type II cells. Electron microscopy further demonstrated the accumulation of lamellar bodies and the co-localization of lamellar bodies with autophagosomes in the cytoplasm of alveolar epithelial type II cells. The inhibition of autophagy with 3-Methyladenine and knockdown of Atg7 abolished hyperoxia-induced SP-C accumulation in the cytoplasm. Furthermore, inhibition of JNK signaling with SP600125 suppressed hyperoxia-induced Atg7 expression and SP-C accumulation. These findings suggest that hyperoxia triggers autophagy via JNK signaling-mediated Atg7 expression, which promotes the accumulation of SP-C within alveolar epithelial type II cells. Our data provide a potential approach for hyperoxic lung injury therapy by targeted pharmacological inhibition of autophagic pathway. Springer Science+Business Media New York, 2015 Hyperoxia nationallicence Autophagy nationallicence Surfactant protein C nationallicence Alveolar type II cells nationallicence Zhang Liang Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut Zhao Shuang Department of Pediatrics, The Fourth People Hospital of Shenyang, 20 Huang He Street, 110003, Shenyang, Liaoning, China aut Yuan Li-Jie Department of Biochemistry and Molecular Biology, Harbin Medical University, Daqing Campus, 163319, Daqing, China aut Wu Hong-Min Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut Jiang Hong Department of Pediatrics, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut Zhao Shi-Meng Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut Luo Gang Department of Pediatrics, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut Xue Xin-Dong Department of Pediatrics, Shengjing Hospital of China Medical University, 36 San Hao Street, 110004, Shenyang, Liaoning, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 181-189 0300-8177 408:1-2<181 2015 408 11010 https://doi.org/10.1007/s11010-015-2494-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2494-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Liang Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut NATIONALLICENCE 700 1- Zhao Shuang Department of Pediatrics, The Fourth People Hospital of Shenyang, 20 Huang He Street, 110003, Shenyang, Liaoning, China aut NATIONALLICENCE 700 1- Yuan Li-Jie Department of Biochemistry and Molecular Biology, Harbin Medical University, Daqing Campus, 163319, Daqing, China aut NATIONALLICENCE 700 1- Wu Hong-Min Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut NATIONALLICENCE 700 1- Jiang Hong Department of Pediatrics, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut NATIONALLICENCE 700 1- Zhao Shi-Meng Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut NATIONALLICENCE 700 1- Luo Gang Department of Pediatrics, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, 110001, Shenyang, Liaoning, China aut NATIONALLICENCE 700 1- Xue Xin-Dong Department of Pediatrics, Shengjing Hospital of China Medical University, 36 San Hao Street, 110004, Shenyang, Liaoning, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 181-189 0300-8177 408:1-2<181 2015 408 11010