RUNX3-dependent oxidative epithelial-to-mesenchymal transition in methamphetamine-induced chronic lung injury
| Autor: | Xin Wang, Lei Chen, Lin Cheng, Ying-Jian Gu, Mei-Jia Zhu, Lin Shi, Bing-Yang Liu, Ming-Yuan Zhou, Yun Wang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Epithelial-Mesenchymal Transition Oxidative phosphorylation medicine.disease_cause Biochemistry Methamphetamine 03 medical and health sciences 0302 clinical medicine Western blot medicine Animals Humans Epithelial–mesenchymal transition Rats Wistar Lung chemistry.chemical_classification Gene knockdown Reactive oxygen species Original Paper medicine.diagnostic_test Chemistry Cell Biology Lung Injury digestive system diseases Rats Oxidative Stress 030104 developmental biology medicine.anatomical_structure Core Binding Factor Alpha 3 Subunit A549 Cells 030220 oncology & carcinogenesis Alveolar Epithelial Cells embryonic structures Chronic Disease Cancer research Immunohistochemistry Reactive Oxygen Species Oxidative stress |
| Zdroj: | Cell Stress Chaperones |
| ISSN: | 1466-1268 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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