Lethal (2) giant larvae regulates pleural mesothelial cell polarity in pleural fibrosis

Lin-Jie Song; Li-Ling Zhou; Meng Wang; Fei Liu; Liang Xiong; Fei Xiang; Fan Yu; Xin-Liang He; Juan-Juan Xu; Huan-Zhong Shi; Jian-Bao Xin; Hong Ye; Wan-Li Ma

doi:10.1016/j.bbamcr.2018.05.013

Lethal (2) giant larvae regulates pleural mesothelial cell polarity in pleural fibrosis

Biochim Biophys Acta Mol Cell Res. 2018 Sep;1865(9):1201-1210. doi: 10.1016/j.bbamcr.2018.05.013. Epub 2018 May 26.

Authors

Lin-Jie Song¹, Li-Ling Zhou¹, Meng Wang², Fei Liu², Liang Xiong³, Fei Xiang³, Fan Yu³, Xin-Liang He³, Juan-Juan Xu³, Huan-Zhong Shi⁴, Jian-Bao Xin³, Hong Ye⁵, Wan-Li Ma⁶

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
² Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Respiratory Diseases, Ministry of Health of China, Wuhan 430030, China.
⁴ Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
⁵ Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Respiratory Diseases, Ministry of Health of China, Wuhan 430030, China. Electronic address: yehmwl@hust.edu.cn.
⁶ Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Respiratory Diseases, Ministry of Health of China, Wuhan 430030, China. Electronic address: whmawl@aliyun.com.

PMID: 29842893
DOI: 10.1016/j.bbamcr.2018.05.013

Abstract

Pleural fibrosis is barely reversible and the underlying mechanisms are poorly understood. Pleural mesothelial cells (PMCs) which have apical-basal polarity play a key role in pleural fibrosis. Loss of cell polarity is involved in the development of fibrotic diseases. Partition defective protein (PAR) complex is a key regulator of cell polarity. However, changes of PMC polarity and PAR complex in pleural fibrosis are still unknown. In this study, we observed that PMC polarity was lost in fibrotic pleura. Next we found increased Lethal (2) giant larvae (Lgl) bound with aPKC and PAR-6B competing against PAR-3A in PAR complex, which led to cell polarity loss. Then we demonstrated that Lgl1 siRNA prevented cell polarity loss in PMCs, and Lgl1 conditional knockout (ER-Cre^+/-Lgl1^flox/flox) attenuated pleural fibrosis in a mouse model. Our data indicated that Lgl1 regulates cell polarity of PMCs, inhibition of Lgl1 and maintenance of cell polarity in PMCs could be a potential therapeutic treatment approach for pleural fibrosis.

Keywords: Lethal (2) giant larvae (Lgl); Partition defective protein (PAR) complex; Pleural fibrosis; Pleural mesothelial cells (PMCs); Polarity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Animals
Cell Line
Cell Polarity
Disease Models, Animal
Epithelial Cells / cytology*
Epithelial Cells / metabolism
Female
Fibrosis
Gene Knockout Techniques
Glycoproteins / genetics*
Glycoproteins / metabolism*
Humans
Male
Mice
Pleura / metabolism
Pleura / pathology*
Protein Kinase C / metabolism
Rats

Substances

Adaptor Proteins, Signal Transducing
Glycoproteins
LGL1 protein, mouse
PKC-3 protein
Protein Kinase C