Changes in the number of CD31⁻CD45⁻Sca-1⁺ cells and Shh signaling pathway involvement in the lungs of mice with emphysema and relevant effects of acute adenovirus infection

Abstract

Background

COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31⁻CD45⁻Sca-1⁺ cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI).

Materials and methods

BALB/c mice were treated with CSE by intraperitoneal injection and/or adenovirus endotracheal instillation at different time points for 28 days. Lung function, lung histomorphology, CD31⁻CD45⁻Sca-1⁺ cell count, and expression levels of major components in the Shh signaling pathway in the lungs were measured.

Results

CSE intraperitoneal injection and adenovirus endotracheal instillation successfully induced emphysema and AAI in mice, respectively. In the lungs of emphysema mice, both the number of CD31⁻CD45⁻Sca-1⁺ cells and expression levels of Shh signaling pathway molecules were reduced. However, AAI increased the number of inhibited CD31⁻CD45⁻Sca-1⁺ cells and activated the suppression of the Shh signaling pathway.

Conclusion

Both CD31⁻CD45⁻Sca-1⁺ cell numbers and Shh signaling pathway expression levels were downregulated in the lungs of emphysema mice induced by CSE intraperitoneal injection, which likely contributes to the pathogenesis of emphysema. Additionally, these inhibited lung CD31⁻CD45⁻Sca-1⁺ cells and Shh signaling pathway molecules were upregulated during AAI, indicating that they play a protective role in the epithelial repair process after AAI injury.

Keywords:

• emphysema
• stem cells
• lung CD31⁻CD45⁻Sca-1⁺ cells
• sonic hedgehog signaling pathway
• adenovirus

Acknowledgments

This work was supported by the China National Science Foundation (Nos 81200026, 81370143, 81270100).

Author contributions

Minhua Deng contributed to the study design and most of the research work. Jinhua Li contributed to the animal model establishment and morphological assessment. Ping Chen and Ye Gan coordinated the study. Yan Chen contributed to the flow cytometry and data analysis. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.