The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells
Xiaoman Li, Liang Wang, Jialin Hao, Qingfeng Zhu, Min Guo, Changjing Wu, Sihui Li, Qiqiang Guo, Qiuhong Ren, Ning Bai, Fei Yi, Bo Jiang, Wenyu Zhang, Yanling Feng, Hongde Xu, Han Jiang, Xiao‐Yue Zhai, Guohua Zhang, Hong‐Long Ji, Xuesong Yang, Dan Zhang, Jianhua Fu, Jianjun Chang, Xiaoyu Song, Liu Cao
Abstract
The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosomerelated organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubuleassociated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood.