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Application of precision-cut lung slice technology to study the role of DDR2 in pulmonary fibrosis

HUANG Xi-Hui¹, CHENG Tao², MOU Ling¹, BO Xin³, WEI Xin-Ru^1,4,*

¹State Key Laboratory of Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China；²Shangrao People’s Hospital, Shangrao 334000, China；³Department of Biochemistry and Molecular Biology, School of Basic Medicine, Air Force Military Medical University, Xi’an 710032, China；⁴Shenzhen International Institute for Biomedical Research, Shenzhen 518000, China

Abstract

Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor β1 (TGF-β1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-β1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.

Key words: precision-cut lung slice; pulmonary fibrosis; DDR2; Cre-LoxP system

Received: 　　Accepted:

Corresponding author: 魏新茹　　E-mail: weixinru2012@163.com

Citing This Article：

HUANG Xi-Hui, CHENG Tao, MOU Ling, BO Xin, WEI Xin-Ru. Application of precision-cut lung slice technology to study the role of DDR2 in pulmonary fibrosis. Acta Physiol Sin 2023; 75 (4): 512-520 (in Chinese with English abstract).