Related Experiment Video
Updated: Dec 14, 2025
Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition
Published on: March 3, 2023
RUNX3-dependent oxidative epithelial-to-mesenchymal transition in methamphetamine-induced chronic lung injury
Lin Shi1, Bing-Yang Liu2, Xin Wang1
1Department 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.
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.
Insights
Methamphetamine (MA) lung injury involves oxidative epithelial-to-mesenchymal transition (EMT). RUNX3 is crucial, as its knockdown worsens MA-induced EMT and lung damage by affecting oxidative stress and TGF-β signaling.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Cell Biology
Background:
- Methamphetamine (MA) abuse is a leading cause of fatal lung toxicity.
- The precise mechanisms underlying MA-induced lung injury, particularly epithelial-to-mesenchymal transition (EMT), remain poorly understood.
Purpose of the Study:
- To investigate whether MA induces EMT in lung tissue.
- To determine the role of RUNX3 in MA-induced oxidative EMT and chronic lung injury.
Main Methods:
- Rats were exposed to MA chronically; lung tissues were analyzed morphologically and via Western blot.
- Cultured alveolar epithelial cells were treated with MA, N-acetyl cysteine (NAC), or RUNX3 knockdown, followed by flow cytometry, Western blot, and immunohistochemistry.
Main Results:
- Chronic MA exposure led to lung structural changes, oxidative stress, and pulmonary EMT.
- N-acetyl cysteine (NAC) increased RUNX3 expression and mitigated EMT.
- RUNX3 knockdown exacerbated MA-induced EMT by activating RUNX3-dependent TGF-β signaling and increasing reactive oxygen species (ROS).
Conclusions:
- RUNX3 plays a critical role in regulating oxidative stress and EMT in MA-induced chronic lung injury.
- RUNX3 may be a key therapeutic target for mitigating methamphetamine-related lung damage.
