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

Abstract

BackgroundInhaled 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.ResultsUsing whole-body dynamic inhalation model, we studied the interactions between aluminum oxide nanoparticles (Al2O3 NPs) and the pulmonary system in vivo. We found that seven-day-exposure to Al2O3 NPs resulted in emphysema and small airway remodeling in murine lungs, accompanied by enhanced inflammation and apoptosis. Al2O3 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.ConclusionIn summary, our studies show that inhibition of PTPN6 plays a critical role in Al2O3 NPs-induced COPD-like lesions.Electronic supplementary materialThe online version of this article (10.1186/s12989-017-0234-0) contains supplementary material, which is available to authorized users.

Pulmonary Toxicity of Realistic Alveolar Deposition Concentrations of Ultrafine Particulate Matters in Human Normal Bronchial Epithelial Cell

“…Ni may come from fuels (Genchi et al 2020). Exposure to Al and Ni is proven to cause COPD-like effects (Li et al 2017) and pulmonary cancer (Genchi et al 2020). Moreover, high Fe serum concentration have been detected in COPD patients (Asker et al 2018).…”

Effects of Ambroxol Hydrochloride on Lung Tissue Cell Apoptosis and Vascular Remodeling in Rats with Smoke Induced Chronic Obstructive Pulmonary Disease

“…Masubuchi et al confirmed that inhibition of apoptosis in lung tissue of COPD mice can significantly inhibit the reduction of transient potential in lung tissue and improve its symptoms [16] . Li et al found that reducing the apoptosis rate of COPD injured mice can significantly improve the autoimmune ability of mice and shorten the recovery period [17] . Sun et al reported that improving the apoptosis of pulmonary microvessels can significantly improve the COPD injury of patients and prevent the deterioration of lung tissue [4] .…”

Potential Toxic Effects of Aluminum Nanoparticles: An overview

“…Treating male rats orally with three successive doses of AlNPs (25 mg/kg), resulted in significant DNA damage (increase in tail intensity) in bone marrow cells . Li et al (2017) found that treatment of mice with AlNPs (0.4 or 2 mg/m 3 ) through inhalation for seven days resulted in emphysema and small airway remodeling in lungs, accompanied with enhanced inflammation and apoptosis. Exposure to AlNPs led to inhibition of protein tyrosine phosphatase, non-receptor type 6 (PTPN6) and phosphorylation of Signal transducer and activator of transcription 3 (STAT3), involved in the development of pulmonary inflammatory disease.…”