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Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells

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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.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81170605).

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Authors and Affiliations

  1. Department of Neonatology, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, Shenyang, 110001, Liaoning, China

    Liang Zhang, Hong-Min Wu & Shi-Meng Zhao

  2. Department of Pediatrics, The Fourth People Hospital of Shenyang, 20 Huang He Street, Shenyang, 110003, Liaoning, China

    Shuang Zhao

  3. Department of Biochemistry and Molecular Biology, Harbin Medical University, Daqing Campus, Daqing, 163319, China

    Li-Jie Yuan

  4. Department of Pediatrics, The First Affiliated Hospital of China Medical University, 155 Nan Jing Northern Street, Shenyang, 110001, Liaoning, China

    Hong Jiang & Gang Luo

  5. Department of Pediatrics, Shengjing Hospital of China Medical University, 36 San Hao Street, Shenyang, 110004, Liaoning, China

    Xin-Dong Xue

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  1. Liang Zhang
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Correspondence to Hong-Min Wu.

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Zhang, L., Zhao, S., Yuan, LJ. et al. Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells. Mol Cell Biochem 408, 181–189 (2015). https://doi.org/10.1007/s11010-015-2494-z

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  • DOI: https://doi.org/10.1007/s11010-015-2494-z

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