Molecular Mechanisms Underlying the Nephrotoxicity of Cisplatin, Lead Acetate and Cyclosporine: Key Roles of Myc and Smad4Hassan Askari1, Ehsan Raeis Abdullahi1, Vahdat Poortahmasebi2, Danya Abazari3, Matin Asghari4, Solmaz Sadeghi5, Mohammad Foad Abazari6, Reza Mahmoudi7, Amir Savardashtaki8and Mansour Poorebrahim5*
- *Corresponding Author:
- Mansour Poorebrahim
Department of Medical Biotechnology
School of Advanced Technologies in Medicine
Tehran University of Medical Sciences
E-mail: [email protected]
Received date: Febraury 18, 2017; Accepted date: March 24, 2017; Published date: March 31, 2017
Citation: Askari H, Abdullahi ER, Poortahmasebi V, Abazari D, Asghari M, et al. (2017) Molecular Mechanisms Underlying the Nephrotoxicity of Cisplatin, Lead Acetate and Cyclosporine: Key Roles of Myc and Smad4. Biol Syst Open Access 6:176. doi:10.4172/2329-6577.1000176
Copyright: © 2017 Askari H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
It is well documented that use of Cisplatin, Lead acetate and Cyclosporine in the chemotherapy and medical interventions is highly associated with nephrotoxicity and interrelated comorbidities. Here, we proposed the possible molecular mechanisms responsible for nephrotoxicity of these compounds. We utilized the microarray dataset GSE59913 consisting of approximately 600 different compounds profiled in up to 8 different tissues. After analysis with GEO2R, gene expression profiles of three aforementioned compounds were integrated with protein-protein interactions (PPI) networks and topological properties of the networks were measured using Cytoscape software. We found several key genes and signaling pathways that seem to be involved in nephrotoxicity of the examined compounds. Myc and Smad4 were identified as principal players of three compounds’ nephrotoxicity through various pathways. Our results revealed the critical functions of Il2, Jak-Stat, Mapk-Pi3k, TGFβ and Ca2+ signaling pathways as well as novel biomarkers that may mediate the nephrotoxicity of Cisplatin, Lead acetate and Cyclosporine. The significantly altered genes in the compound-treated samples were substantially correlated with regulation of cell proliferation, apoptosis, inflammatory responses and homeostatic processes. This study reveals the important hub genes, biological networks and key pathways as well as novel biomarkers involved in nephrotoxicity of Cisplatin, Lead acetate and Cyclosporine.