Lung toxicity is the main cause of the death from methamphetamine (MA) abuse, but its mechanism has remained unclear. The purpose of our study was to investigate if MA can induce epithelial-to-mesenchymal transition (EMT) and if RUNX3 is involved in oxidative EMT in MA-induced chronic lung injury. The rats were divided into the control group and MA group. Extracted lungs were used for morphological measurements and Western blot. The alveolar epithelial cells were cultured or transfected and then treated with MA or/and N-acetyl cysteine (NAC) followed by flow cytometry, Western blot, and immunohistochemistry. Chronic exposure to MA resulted in the lower growth ratio of weight, increased right ventricular index, thickened alveolar walls, and reduced number of alveolar sacs. Long-term administration with MA caused oxidative stress and pulmonary EMT. NAC increased RUNX3 and alleviated EMT. However, after knockdown of RUNX3, reactive oxygen species (ROS) levels were significantly upregulated, indicating that RUNX3 was closely related to oxidative stress. Knockdown of RUNX3 aggravated MA-induced EMT by activating RUNX3-dependent TGF-β signaling. Therefore, RUNX3 may be the key to oxidative EMT in methamphetamine-induced chronic lung injury.

中文翻译：

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甲基苯丙胺诱导的慢性肺损伤中RUNX3依赖性氧化上皮间质转化。


肺毒性是甲基苯丙胺（MA）滥用导致死亡的主要原因，但其机制仍不清楚。我们研究的目的是探讨 MA 是否可以诱导上皮间质转化 (EMT)，以及 RUNX3 是否参与 MA 诱导的慢性肺损伤中的氧化 EMT。将大鼠分为对照组和MA组。提取的肺用于形态学测量和蛋白质印迹。培养或转染肺泡上皮细胞，然后用MA或/和N-乙酰半胱氨酸（NAC）处理，然后进行流式细胞术、蛋白质印迹和免疫组织化学分析。长期暴露于MA会导致体重增长率降低、右心室指数增加、肺泡壁增厚、肺泡囊数量减少。长期给予MA会引起氧化应激和肺EMT。 NAC 增加 RUNX3 并减轻 EMT。然而，敲低RUNX3后，活性氧（ROS）水平显着上调，表明RUNX3与氧化应激密切相关。 RUNX3 的敲低通过激活 RUNX3 依赖性 TGF-β 信号传导加剧了 MA 诱导的 EMT。因此，RUNX3可能是甲基苯丙胺诱导的慢性肺损伤中氧化EMT的关键。