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.

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.