Related Experiment Video
Updated: May 10, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Analyzing molecular signatures in preeclampsia and fetal growth restriction: Identifying key genes, pathways, and
Muhammad Bilal Azmi1, Mushyeda Fatima Nasir2, Uzma Asif3
1Computational Biochemistry Research Laboratory, Department of Biochemistry, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.
Insights
This study identified PTGS2 as a key gene linking preeclampsia (PE) and intrauterine growth restriction (IUGR). Flavoxate shows promising therapeutic potential for PE and IUGR, potentially aiding in preterm birth management.
Area of Science:
- Reproductive biology
- Genomics
- Pharmacology
Background:
- Preeclampsia (PE) and intrauterine growth restriction (IUGR) are linked to maternal conditions and preterm birth (PTB).
- The molecular mechanisms connecting PE and IUGR remain unclear.
- This study investigates the molecular underpinnings of PE and PE with IUGR.
Purpose of the Study:
- To identify key genes and molecular pathways associated with PE and PE with IUGR.
- To explore potential therapeutic targets and drug interactions for these conditions.
- To analyze the molecular relationship between PE and IUGR.
Main Methods:
- Utilized RNA sequencing datasets (GSE148241, GSE114691) for differential gene expression analysis.
- Constructed protein-protein interaction networks and performed cluster analysis.
- Docked potential therapeutic compounds (flavonoids, PTB drugs) with identified hub proteins and conducted molecular dynamic simulations.
Main Results:
- Identified eight hub genes in PE (e.g., PTGS2, ENG) and nine in PE + IUGR (e.g., PTGS2, FGF7).
- PTGS2 was identified as a common hub gene in both conditions.
- Flavoxate exhibited strong binding affinity to PTGS2 with favorable pharmacokinetic properties and stable molecular dynamics.
Conclusions:
- The study highlights PTGS2 as a crucial gene in the pathophysiology of PE and IUGR.
- Flavoxate demonstrates potential as a therapeutic agent for PE and IUGR.
- Findings may inform strategies for managing preterm birth associated with PE and IUGR.
Background:
Intrauterine growth restriction (IUGR) and preeclampsia (PE) are intricately linked with specific maternal health conditions, exhibit shared placental abnormalities, and play pivotal roles in precipitating preterm birth (PTB) incidences. However, the molecular mechanism underlying the association between PE and IUGR has not been determined. Therefore, we aimed to analyze the data of females with PE and those with PE + IUGR to identify the key gene(s), their molecular pathways, and potential therapeutic interactions.
Methods:
In this study, a comprehensive relationship analysis of both PE and PE + IUGR was conducted using RNA sequence datasets. Using two datasets (GSE148241 and GSE114691), differential gene expression analysis via DESeq2 through R-programming was performed. Gene set enrichment analysis was performed using ClusterProfiler, protein‒protein interaction (PPI) networks were constructed, and cluster analyses were conducted using String and MCODE in Cytoscape. Functional enrichment analyses of the resulting subnetworks were performed using ClueGO software. The hub genes were identified under both conditions using the CytoHubba method. Finally, the most common hub protein was docked against a library of bioactive flavonoids and PTB drugs using the PyRx AutoDock tool, followed by molecular dynamic (MD) simulation analysis. Pharmacokinetic analysis was performed to determine the ADMET properties of the compounds using pkCSM.
Results:
We identified eight hub genes highly expressed in the case of PE, namely, PTGS2, ENG, KIT, MME, CGA, GAPDH, GPX3, and P4HA1, and the network of the PE + IUGR gene set demonstrated that nine hub genes were overexpressed, namely, PTGS2, FGF7, FGF10, IL10, SPP1, MPO, THBS1, CYBB, and PF4. PTGS2 was the most common hub gene found under both conditions (PE and PEIUGR). Moreover, the greater (-9.1 kcal/mol) molecular binding of flavoxate to PTGS2 was found to have satisfactory pharmacokinetic properties compared with those of other compounds. The flavoxate-bound PTGS2 protein complex remained stable throughout the simulation; with a ligand fit to protein, i.e., a RMSD ranging from ∼2.0 to 4.0 Å and a RMSF ranging from ∼0.5 to 2.9 Å, was observed throughout the 100 ns analysis.
Conclusion:
The findings of this study may be useful for treating PE and IUGR in the management of PTB.
