Microarray gene expression analysis of the human airway in patients exposed to sulfur mustard
Ali Najafi1, Ali Masoudi-Nejad, Abbas Ali Imani Fooladi
1Chemical Injuries Research Center, Systems Biology Institute, Genomics Division, Baqiyatallah University of Medical Sciences , Tehran , Iran .
Abstract:
There is much data about the acute effects of sulfur mustard gas on humans, animals and cells. But less is known regarding the molecular basics of chronic complications in humans. Basically, mustard gas, as an alkylating agent, causes several chronic problems in the eyes, skin and more importantly in the pulmonary system which is the main cause of death. Although recent proteomic research has been carried out on bronchoalveolar lavage (BAL) and serum, but high-throughput transcriptomics have not yet been applied to chronic airway remodeling. This is the first cDNA-microarray report on the chronic human mustard lung disease, 25 years after exposure during the Iran-Iraq war. Microarray transcriptional profiling indicated that a total of 122 genes were significantly dysregulated in tissues located in the airway of patients. These genes are associated with the extracellular matrix components, apoptosis, stress response, inflammation and mucus secretion.
Insights
Sulfur mustard exposure causes chronic lung disease. This study reveals 122 dysregulated genes in airway tissues, linked to extracellular matrix, apoptosis, inflammation, and mucus, offering insights into long-term health effects.
Area of Science:
- Toxicology
- Molecular Biology
- Pulmonary Medicine
Background:
- Sulfur mustard (SM) is an alkylating agent causing acute and chronic health issues, particularly in the lungs.
- Chronic complications of SM exposure, especially molecular mechanisms in the airway, remain poorly understood.
- Previous research focused on proteomics; high-throughput transcriptomics for chronic airway remodeling is lacking.
Purpose of the Study:
- To investigate the molecular basis of chronic lung disease following sulfur mustard exposure using transcriptomics.
- To identify dysregulated genes in airway tissues of individuals with chronic mustard lung disease.
Main Methods:
- Utilized cDNA-microarray technology for transcriptional profiling.
- Analyzed airway tissue samples from patients with chronic mustard lung disease, 25 years post-exposure.
- Compared gene expression patterns to identify significantly dysregulated genes.
Main Results:
- Identified 122 significantly dysregulated genes in the airway tissues of patients.
- These genes are associated with key biological processes including extracellular matrix remodeling, apoptosis, stress response, inflammation, and mucus secretion.
- This is the first report using transcriptomics to study chronic human mustard lung disease.
Conclusions:
- Transcriptional profiling reveals significant gene dysregulation in chronic mustard lung disease.
- Identified genes provide molecular insights into airway remodeling, inflammation, and mucus production post-sulfur mustard exposure.
- Findings contribute to understanding the long-term pulmonary consequences of chemical warfare agent exposure.
