Identification of key molecular targets and mechanism of action in acute kidney injury by integrating network pharmacology and molecular docking

Acute kidney injury (AKI) is a frequent renal complication in surgical settings. This study aimed to identify key molecular targets for AKI and to elucidate the mechanism of action of drugs that targeted these molecular targets. Potential molecular targets for AKI were identified by integrating data from DisGeNET, Comparative Toxicogenomics Database (CTD), Swiss Target Prediction (STP), and differential expression analysis between AKI and normal samples. Protein-protein interaction (PPI) network was constructed using the STRING online tool and analyzed with Cytoscape software to identify densely connected regions and compute topology parameters, thereby revealing hub genes among the potential molecular targets. Immune characteristics of AKI samples were assessed using ESTIMATE and ssGSEA algorithms, and Pearson correlation analysis was performed to evaluate the association between the 15 hub genes and immune characteristics. A total of 71 potential molecular targets for AKI were screened, 31 of which were directly related associated with the AKI phenotype. PPI network analysis revealed four functional modules comprising 39 potential molecular targets of AKI. From these, 15 hub genes with the highest degree, betweenness centrality, and closeness centrality were selected. Molecular docking simulations indicated that vasopressin bound stably to CCND1, one of the hub genes for AKI, suggesting a specific interaction between the two. This study identified 15 potential molecular targets for AKI and demonstrated a stable binding conformation between vasopressin and CCND1. The current study provided mechanistic insight into efficacy of vasopressin in treating AKI.