Related Experiment Video
Updated: Aug 18, 2025
Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
Published on: October 28, 2022
Protein-protein interactions between RUNX3 and ZEB1 in chronic lung injury induced by methamphetamine abuse
Ning Bao1, Lin Cheng2, Yun Wang3
1Department of Anesthesiology, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, Guangdong, China.
Abstract:
Methamphetamine (MA) is the most common and highly addictive substance abuse drug. Runt-related transcription factor 3 (RUNX3) and Zinc finger E-box-binding homeobox 1 (ZEB1) are associated with lung inflammation and fibrosis. However, the protein-protein interactions (PPIs) between RUNX3 and ZEB1 and its involvement in MA-induced chronic lung injury is still unclear. In this study, we evaluated lung injury using echocardiography, hematoxylin and eosin staining, and western blot analysis. The viability of alveolar epithelial cells (AECs) was assessed using cell counting kit-8. Molecular Operating Environment software, Search Tool for the Retrieval of Interacting Genes/Proteins database, co-immunoprecipitation, assay and confocal immunofluorescence assay were used to predict and identify the PPIs between RUNX3 and ZEB1. The expression of RUNX3 and ZEB1 were knockdown in AECs using siRNA. The results revealed that MA exposure increased the peak blood flow velocity of the pulmonary artery and the acceleration time of pulmonary artery blood flow. Further, exposure to MA also causes adhesion and fusion of the alveolar walls and altered AEC activity. A decrease in the expression of RUNX3 and an increase in the expression of ZEB1 and its downstream signaling molecules were observed on MA exposure. The PPIs between RUNX3 and ZEB1 were identified. Further, an increase in the protein binding rate of RUNX3-ZEB1 was observed in MA-induced lung injury. These results show interactions between RUNX3 and ZEB1. RUNX3 protects against lung injury; however, ZEB1 expression and the PPIs between ZEB1 and RUNX3 has deleterious effects on chronic lung injury induced by MA exposure. Our results provide a new therapeutic approach for the treatment of chronic lung injury due to MA exposure.
Insights
Methamphetamine (MA) exposure causes chronic lung injury by altering alveolar epithelial cells. The interaction between RUNX3 and Zinc finger E-box-binding homeobox 1 (ZEB1) plays a key role in this damage.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Toxicology
Background:
- Methamphetamine (MA) abuse is a significant public health issue, often leading to chronic lung injury.
- Runt-related transcription factor 3 (RUNX3) and Zinc finger E-box-binding homeobox 1 (ZEB1) are implicated in lung inflammation and fibrosis.
- The specific protein-protein interactions (PPIs) between RUNX3 and ZEB1 in MA-induced lung injury remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of protein-protein interactions between RUNX3 and ZEB1 in methamphetamine-induced chronic lung injury.
- To elucidate the molecular mechanisms underlying MA-induced lung damage involving RUNX3 and ZEB1.
- To identify potential therapeutic targets for mitigating MA-induced lung injury.
Main Methods:
- Lung injury was assessed using echocardiography, hematoxylin and eosin staining, and Western blot.
- Alveolar epithelial cell (AEC) viability was evaluated using cell counting kit-8.
- Protein-protein interactions between RUNX3 and ZEB1 were predicted and identified using computational tools, co-immunoprecipitation, and confocal immunofluorescence assays. siRNA was used to knockdown RUNX3 and ZEB1 expression in AECs.
Main Results:
- MA exposure led to pulmonary artery hypertension and altered alveolar structure and AEC activity.
- RUNX3 expression decreased, while ZEB1 expression and its downstream signaling molecules increased following MA exposure.
- Direct protein-protein interactions between RUNX3 and ZEB1 were confirmed, with increased binding observed in MA-induced lung injury.
Conclusions:
- RUNX3 exhibits a protective role against lung injury, whereas increased ZEB1 expression and its interaction with RUNX3 exacerbate MA-induced chronic lung injury.
- The identified RUNX3-ZEB1 interaction provides a novel molecular target for therapeutic intervention in methamphetamine-induced lung damage.
- Understanding these interactions offers a new therapeutic strategy for treating chronic lung injury resulting from MA abuse.
More Related Videos
06:12Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition
Published on: March 3, 2023
09:16Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019