Exploring the Mechanisms of Lead (II)-Induced Nephrotoxicity via Integrative Bioinformatics Analysis

Lead (Pb), a pervasive environmental toxicant, exerts substantial nephrotoxic effects in mammalian organisms. However, the molecular mechanisms underlying Pb-induced renal toxicity remain poorly elucidated. In this study, we employed an integrative bioinformatics approach to identify pivotal hub genes associated with Pb nephrotoxicity through comprehensive analysis of the GEO data set GSE59913. Comparative transcriptomic analysis of renal tissues from PbAc₂-exposed (600 mg/kg) and control rats identified 541 differentially expressed genes (DEGs), showing predominant enrichment in response to xenobiotic stimulus, signal transduction, and response to toxic substance. Multilayer pathway analysis revealed significant convergence on metabolic homeostasis networks, PI3K-Akt, AMPK, MAPK, Jak-STAT, PPAR, and cytokine-cytokine receptor interaction pathways. Utilizing protein-protein interaction networks, we identified ten pivotal hub genes implicated in Pb-induced nephrotoxicity-including IL6 (interleukin 6), CDK1 (cyclin-dependent kinase 1), and CCNA2 (cyclin-A2)-which are functionally associated with IL-17, JAK-STAT, TNF signaling, DNA replication, and cell cycle regulation pathways. This study provides the mechanistic framework for Pb nephrotoxicity, uncovering potential therapeutic targets for environmental heavy metal toxicity.