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- Title
Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells.
- Authors
Zhang, Liang; Luo, Gang; Zhao, Shuang; Jiang, Hong; Yuan, Li-Jie; Xue, Xin-Dong; Zhao, Shi-Meng; Wu, Hong-Min
- 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.
- Subjects
PULMONARY surfactant-associated protein C; AUTOPHAGY; HYPEROXIA; EPITHELIAL cells; BRONCHOPULMONARY dysplasia; NEONATAL diseases; C-Jun N-terminal kinases; ANIMAL models in research
- Publication
Molecular & Cellular Biochemistry, 2015, Vol 408, Issue 1/2, p181
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-015-2494-z