title: Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells.
abstract: 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.
authors.affiliation: Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, Shenyang, 110001, Liaoning, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The Fourth People Hospital of Shenyang, 20 Huang He Street, Shenyang, 110003, Liaoning, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Daqing Campus, Daqing, 163319, China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Yuan
authors.affiliation: Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, Shenyang, 110001, Liaoning, China. hm_wu@hotmail.com.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, Shenyang, 110001, Liaoning, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, Shenyang, 110001, Liaoning, China.
authors.forename: Shi-Meng
authors.initials: SM
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, Shenyang, 110001, Liaoning, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, 36 San Hao Street, Shenyang, 110004, Liaoning, China.
authors.forename: Xin-Dong
authors.initials: XD
authors.lastname: Xue
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy; D015687:Cell Hypoxia; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology*; D020935:MAP Kinase Signaling System; D051379:Mice; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism*; D051381:Rats; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism*
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C; D044764:Ubiquitin-Activating Enzymes
keywords: Alveolar type II cells; Autophagy; Hyperoxia; Surfactant protein C