Journal of Advances in Medical and Biomedical Research

en Identification Biomarkers and Molecular Mechanisms Involved in Lung Transplant Rejection, and Drug Repurposing: A Systems Biology Study Medical Biology Medical Biology مقاله پژوهشی Original Research Article 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. Lung Disease, Transplantation, Systems Biology, Protein-protein Interaction Network, Gene Regulatory Network 525 535 http://journal.zums.ac.ir/browse.php?a_code=A-10-6761-1&slc_lang=en&sid=1 Seyed Amir Mirmotalebisohi armotalebi@yahoo.com 5200319475328460079100 5200319475328460079100 No Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zeinab Dehghan dehghan.m.zeinab@gmail.com 5200319475328460079101 5200319475328460079101 No Dept. of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran Abbas Alibakhshi alibakhshi2630@yahoo.com 5200319475328460079102 5200319475328460079102 No Molecular Medicine Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Fatemeh Yarian f.yarian@gmail.com 5200319475328460079104 5200319475328460079104 No Dept. of Medical Biotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran Hakimeh Zali hakimehzali@gmail.com 5200319475328460079103 5200319475328460079103 Yes Dept. of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran