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RUNX3-dependent oxidative epithelial-to-mesenchymal transition in methamphetamine-induced chronic lung injury

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Cell Stress and Chaperones Aims and scope

Abstract

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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This research was funded by the National Natural Science Foundation of China (Nos. 81973404 and 81503058), Department of Education of Liaoning Province (No. JC2019034), and Natural Science Foundation of Liaoning Province (No. 2014021065).

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Author notes

  1. Lin Shi and Bing-Yang Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, People’s Republic of China

    Lin Shi, Xin Wang, Mei-Jia Zhu, Lei Chen, Ming-Yuan Zhou, Ying-Jian Gu, Lin Cheng & Yun Wang

  2. Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, People’s Republic of China

    Bing-Yang Liu

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  1. Lin Shi
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Correspondence to Yun Wang.

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All animals’ experimental procedures comply with the guidelines of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH), with the approval of the Institutional Animal Care and Use Committee of China Medical University (IACUC Issue No. CMU2019215).

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The authors declare that they have no competing interests.

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Shi, L., Liu, BY., Wang, X. et al. RUNX3-dependent oxidative epithelial-to-mesenchymal transition in methamphetamine-induced chronic lung injury. Cell Stress and Chaperones 25, 793–802 (2020). https://doi.org/10.1007/s12192-020-01133-w

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