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. Using 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. In summary, our studies show that inhibition of PTPN6 plays a critical role in Al2O3 NPs-induced COPD-like lesions.

中文翻译：

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PTPN6的抑制通过激活STAT途径加剧了小鼠中氧化铝纳米颗粒诱导的COPD样病变。

吸入的纳米颗粒可以沉积在深肺中，在那里它们与肺细胞相互作用。尽管对肺部纳米毒性进行了大量研究，但尚未确定具体的纳米材料诱导的肺损伤的详细分子机制。使用全身动态吸入模型，我们研究了氧化铝纳米颗粒（Al2O3 NPs）与体内肺系统之间的相互作用。我们发现，暴露于Al2O3 NP的7天导致小鼠肺气肿和小气道重塑，并伴有炎症和凋亡的增强。Al2O3 NPs暴露导致PTPN6的抑制和STAT3的磷酸化，最终导致凋亡标记PDCD4的表达增加。挽救PTPN6的表达或使用STAT3抑制剂可有效保护鼠肺免受炎症和细胞凋亡的侵害，部分是由于诱发了慢性阻塞性肺疾病（COPD）样效应。总之，我们的研究表明，对PTPN6的抑制在Al2O3 NPs诱导的COPD样病变中起关键作用。