1. Academic Validation
  2. Impaired AT2 to AT1 cell transition in PM2.5-induced mouse model of chronic obstructive pulmonary disease

Impaired AT2 to AT1 cell transition in PM2.5-induced mouse model of chronic obstructive pulmonary disease

  • Respir Res. 2022 Mar 25;23(1):70. doi: 10.1186/s12931-022-01996-w.
Hongjiao Yu  # 1 Yingnan Lin  # 1 Yue Zhong  # 1 Xiaolan Guo 1 Yuyin Lin 1 Siqi Yang 1 Jinglin Liu 1 Xinran Xie 1 Yaowei Sun 1 Dong Wang 2 Bing Li 1 Pixin Ran 3 Jianwei Dai 4 5 6
Affiliations

Affiliations

  • 1 Guangzhou Medical University-Guangzhou Institute of Biomedicine and Health (GMU-GIBH) Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 510000, People's Republic of China.
  • 2 State Key Lab of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People's Republic of China.
  • 3 State Key Lab of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People's Republic of China. pxran@gzhmu.edu.cn.
  • 4 Guangzhou Medical University-Guangzhou Institute of Biomedicine and Health (GMU-GIBH) Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 510000, People's Republic of China. daijw@gzhmu.edu.cn.
  • 5 State Key Lab of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People's Republic of China. daijw@gzhmu.edu.cn.
  • 6 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Qingyuan, 511500, People's Republic of China. daijw@gzhmu.edu.cn.
  • # Contributed equally.
Abstract

Background: Particular matter 2.5 (PM2.5) is one of the most important air pollutant, and it is positively associated with the development of chronic obstructive pulmonary disease (COPD). However, the precise underlying mechanisms through which PM2.5 promotes the development of COPD remains largely unknown.

Methods: Mouse alveolar destruction were determined by histological analysis of lung tissues and lung function test. Alveolar type II cells (AT2) to alveolar type I cells (AT1) transition in PM2.5-induced COPD mouse model was confirmed via immunofluorescence staining and qPCR analysis. The differentially expressed genes in PM2.5-induced COPD mouse model were identified by RNA-sequencing of alveolar epithelial organoids and generated by bioinformatics analysis.

Results: In this study, we found that 6 months exposure of PM2.5 induced a significantly decreased pulmonary compliance and resulted in pulmonary emphysema in mice. We showed that PM2.5 exposure significantly reduced the AT2 to AT1 cell transition in vitro and in vivo. In addition, we found a reduced expression of the intermediate AT2-AT1 cell process marker claudin 4 (CLDN4) at day 4 of differentiation in mouse alveolar organoids treated with PM2.5, suggesting that PM2.5 exposure inhibited AT2 cells from entering the transdifferentiation process. RNA-sequencing of mouse alveolar organoids showed that several key signaling pathways that involved in the AT2 to AT1 cell transition were significantly altered including the Wnt signaling, MAPK signaling and signaling pathways regulating pluripotency of stem cells following PM2.5 exposure.

Conclusions: In summary, these data demonstrate a critical role of AT2 to AT1 cell transition in PM2.5-induced COPD mouse model and reveal the signaling pathways that potentially regulate AT2 to AT1 cell transition during this process. Our findings therefore advance the current knowledge of PM2.5-induced COPD and may lead to a novel therapeutic strategy to treat this disease.

Keywords

AT2-to-AT1 transition; Alveolar epithelium; COPD; PM2.5.

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