Identification Biomarkers and Molecular Mechanisms Involved in Lung Transplant Rejection, and Drug Repurposing: A Systems Biology Study

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Article Type:
Research/Original Article (دارای رتبه معتبر)
Abstract:
Background and Objective

 Lung transplantation is a promising  therapy for patients with end-stage lung disease. Pulmonary surfactant is a lipid and protein complex which has  a key role in lung function. Molecular mechanisms mediating in rejection of lung transplantation related to surfactants are not still comprehensively understood. In this study, we applied bioinformatics approaches to identify genes and molecular mechanisms involved in surfactant function in rejection of lung transplantation.

Materials and Methods

 At first, transcriptomics data was extracted and analyzed to construct the protein-protein interaction network and gene regulatory network using Cytoscape. Then, networks analysis were performed to determine hubs, bottlenecks, clusters, and regulatory motifs to identify critical genes and molecular mechanisms involve in surfactant function in rejection of lung transplantation. Finally, critical genes selected for repuposing drugs.

Results

 Analyzing the constructed PPIN and GRN identified SCD, FN1, ICAM1, ITGB8, FOXC1, SIX1, FHL2, KRT5, TFAP2A, GAS5, MALAT1, and lnrCXCR4 as critical genes. Enrichment analysis showed the genes are enriched for pulmonary surfactant metabolism dysfunction, defective CSF2RB causes pulmonary surfactant metabolism dysfunction 4 and 5, Interleukin-4 and Interleukin-13 signaling  may be the mechanisms for surfactant function in rejection of lung transplantation. We predicted some candidate drugs for preventing of lung transplantation rejection such as Sunitinib, Gemcitabine, Oxaliplatin, Hyaluronic acid, … .

Conclusion

 Following our model validation using the existing experimental data, our model suggested critical molecules and candidate medicines involve in  surfactant function in rejection of lung transplantation for furtur investigations.

Language:
English
Published:
Journal of Advances in Medical and Biomedical Research, Volume:31 Issue: 149, Nov-Dec 2023
Pages:
525 to 535
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