Identification of common key regulators in rat hepatocyte cell lines under exposure of different pesticides
Seyed Sajad Sohrabi1, Seyyed Mohsen Sohrabi1, Marzieh Rashidipour2
1Young Researchers and Elite Club, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran.
Abstract:
Pesticides exposure can have harmful effects on human health. The liver is the most common organ of pesticides toxicity due to its major metabolic activity. The molecular mechanism of pesticides effect is complex and is controlled by gene regulatory networks. All components of regulatory networks are controlled by transcription factors and other regulatory elements. Therefore, identification of key regulators through system biology approaches and high-throughput techniques can help to provide comprehensive insights into molecular mechanisms of the pesticide effect. In the current study, a microarray data-set was used to potentially identify molecular mechanisms that regulate gene expression profile of rat hepatocyte cell lines in response to pesticides exposure. Results showed that the number of differentially expressed genes (DEGs) and differentially expressed transcription factors (DE-TFs) were dramatically different among pesticides tested. Results also revealed 205 common DEGs and 11 DE-TFs among pesticides tested. Additionally, we found that six DE-TFs (CREB1, CTNNB1, PPARG, SP1, SRF and STAT3) had the highest number of interactions with other DEGs and acted as the key regulatory genes. The results of this study revealed regulator genes that have the key functions in response to pesticides toxicity in rat liver, which can provide the basis for future studies. Furthermore, these regulatory genes can be used as toxicity biomarkers to improve diagnosis and prognosis.
Insights
This study identified key regulatory genes involved in pesticide toxicity in rat liver cells. These findings can help develop new biomarkers for diagnosing and predicting pesticide-induced liver damage.
Area of Science:
- Toxicology
- Molecular Biology
- Systems Biology
Background:
- Pesticide exposure poses health risks, with the liver being a primary target organ for toxicity.
- Understanding the complex molecular mechanisms of pesticide effects, governed by gene regulatory networks, is crucial.
Purpose of the Study:
- To identify molecular mechanisms regulating gene expression in rat hepatocytes exposed to pesticides.
- To uncover key regulatory genes and transcription factors involved in pesticide toxicity.
Main Methods:
- Utilized microarray data analysis to identify differentially expressed genes (DEGs) and transcription factors (DE-TFs) in rat hepatocytes.
- Applied systems biology approaches to analyze gene regulatory networks.
Main Results:
- Significant differences in DEGs and DE-TFs were observed across different pesticides.
- Identified 205 common DEGs and 11 common DE-TFs among the tested pesticides.
- Discovered six key regulatory transcription factors (CREB1, CTNNB1, PPARG, SP1, SRF, and STAT3) with extensive interactions.
Conclusions:
- Identified critical regulator genes underlying pesticide toxicity in the rat liver.
- These regulatory genes show potential as toxicity biomarkers for improved diagnosis and prognosis of pesticide-induced liver injury.
