Int J Biol Sci 2022; 18(3):1107-1119. doi:10.7150/ijbs.64285 This issue

Research Paper

The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells

Xiaoman Li1,2,3#, Liang Wang4#, Jialin Hao1,2, Qingfeng Zhu1,2, Min Guo1,2, Changjing Wu1*, Sihui Li1, Qiqiang Guo1,2, Qiuhong Ren1, Ning Bai1,2, Fei Yi1,2, Bo Jiang1,2, Wenyu Zhang1, Yanling Feng1,2, Hongde Xu1,2, Han Jiang5, Xiaoyue Zhai1, Guohua Zhang6, Hong-long Ji7, Xuesong Yang8, Dan Zhang9, Jianhua Fu9, Jianjun Chang3, Xiaoyu Song1,2,3✉, Liu Cao1,2✉

1. College of Basic Medical Sciences, China Medical University, Shenyang, China.
2. Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
3. Institute of Health Sciences, China Medical University, Shenyang, China.
4. Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
5. Department of Vascular Surgery, The First affiliated Hospital, China Medical University, Shenyang, China.
6. Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, China.
7. Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, USA.
8. Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
9. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
*Current affiliation: West China Hospital, Sichuan University, China.
#These authors contribute equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Li X, Wang L, Hao J, Zhu Q, Guo M, Wu C, Li S, Guo Q, Ren Q, Bai N, Yi F, Jiang B, Zhang W, Feng Y, Xu H, Jiang H, Zhai X, Zhang G, Ji Hl, Yang X, Zhang D, Fu J, Chang J, Song X, Cao L. The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells. Int J Biol Sci 2022; 18(3):1107-1119. doi:10.7150/ijbs.64285. Available from https://www.ijbs.com/v18p1107.htm

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Abstract

Graphic 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 lysosome-related 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, microtubule-associated 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.

Keywords: autophagy, Atg7, lamellar body, type 2 alveolar cells, LC3B, surfactant protein B