Iranian Biomedical Journal

en Deciphering Molecular Mechanisms of Cutaneous Leishmaniasis, Pathogenesis and Drug Repurposing through Systems Biology Molecular Genetics & Genomics Molecular Genetics & Genomics مقاله کامل Full Length/Original Article <div style="text-align: justify;">Background: Cutaneous leishmaniasis (CL) is a major health problem caused by an intracellular pathogen of the genus Leishmania. CL results in morphologically distinct skin injuries, ranging from nodules to plaques and ulcers, which persist as a recuperating incessant injury depending on the type of contaminating parasite. There is still no effective treatment to reduce the skin lesions in patients infected with CL. The aim of this study was to develop strategies to treat skin lesions in CL patients. Methods: We retrieved the transcriptomic data of skin lesions from patients with CL and normal skin from the gene Expression Omnibus (GEO) database. The protein-protein interaction network (PPIN) was constructed using the STRING database and Cytoscape v3.10.1 software. Critical genes were identified by topological network analysis and cluster detection. Finally, gene ontology and repurposing drugs for critical genes were determined. Results: CD8A, IFNG, IL-6, PTPRC, CCR7, TLR2, GSTA5, CYBB, IL-12RB2, ITGB2, FCGR3A, CTLA4, and IFNG were identified as the critical genes in PPIN and subnetworks. Enrichment analysis revealed that T-cell receptor signaling, toll-like receptor signaling, cytokine-cytokine receptor interaction, graft-versus-host disease, leishmaniasis, chemokine signaling, primary immunodeficiency, and Th17 cell differentiation were the major pathways associated with critical genes. The drug repurposing results identified cyclosporine, rituximab, infliximab, blinatumomab, and methylprednisolone as candidates for treatment of CL. Conclusion: After validating our model with available experimental data, we found that critical molecules and drug candidates play a crucial role in the treatment of skin lesions caused by Leishmania in prospective studies.  </div> Cutaneous leishmaniasis, Gene ontology, Repurpose drug, Systems biology 179 191 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-5777-1&slc_lang=en&sid=1 Fatemeh Saberi fatemeh.saberi82@gmail.com 0009-0007-1659-5992 No Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zeinab Dehghan dehghan.m.zeinab@gmail.com 0000-0003-4787-1287 No Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran Zahra Taheri z.biology87@gmail.com 0009-0008-3140-109X No Department of Biology and Biotechnology, Pavia University, Pavia, Italy Tayyebeh Pilehchi t.pilechi@gmail.com 0009-0009-1967-6741 No Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Hakimeh Zali hakimeh.zali@gmail.com 0000-0003-2770-5759 Yes Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran