Suppression of PTPN6 exacerbates aluminum oxide nanoparticle-induced COPD-like lesions in mice through activation of STAT pathway

Abstract

Background

Inhaled nanoparticles can deposit in the deep lung where they interact with pulmonary cells. Despite numerous studies on pulmonary nanotoxicity, detailed molecular mechanisms of specific nanomaterial-induced lung injury have yet to be identified.

Results

Using whole-body dynamic inhalation model, we studied the interactions between aluminum oxide nanoparticles (Al ₂O ₃ NPs) and the pulmonary system in vivo. We found that seven-day-exposure to Al ₂O ₃ NPs resulted in emphysema and small airway remodeling in murine lungs, accompanied by enhanced inflammation and apoptosis. Al ₂O ₃ NPs exposure led to suppression of PTPN6 and phosphorylation of STAT3, culminating in increased expression of the apoptotic marker PDCD4. Rescue of PTPN6 expression or application of a STAT3 inhibitor, effectively protected murine lungs from inflammation and apoptosis, as well as, in part, from the induction of chronic obstructive pulmonary disease (COPD)-like effects.

Conclusion

In summary, our studies show that inhibition of PTPN6 plays a critical role in Al ₂O ₃ NPs-induced COPD-like lesions.

Electronic supplementary material

The online version of this article (10.1186/s12989-017-0234-0) contains supplementary material, which is available to authorized users.