Identification the Hub Genes of Hirudin Intervention of Diabetic Nephropathy Based On Bioinformatic Analysis and Molecular Docking
Abstract Background: Diabetic nephropathy (DN) is one of the common complications of diabetes, it can cause a disproportionate burden. Leeches are widely used to treat DN in China, and hirudin is the main component of leeches. However, its pharmacological mechanisms and molecular targets are unclear. This work aimed to explore new biomarkers of DN and reveal the mechanism of hirudin in DN. Methods: Expression microarray datas between kidney tissues of DN and control individuals were obtained from the GEO database, and differentially expressed genes were identified as DN-related targets using the robust rank aggregation analysis. The SEA, GeneCards and SwissTargetPrediction databases were used to predict targets of hirudin. A protein-protein interaction network of DN-hirudin was conducted by Cytoscape software. GO and KEGG pathway enrichment analyses were carried out to explore the involved pharmacological mechanism of hirudin in treatment of DN. And molecular docking was adopted to predict the hub targets of hirudin. Results: A total of 30 significant DEGs (16 up- and 14 down-regulated) were identified. ATF3, SLC22A8 and TGF-Β1 are likely as new biomarkers of DN. The 42 candidate targets were identifyed in PPI network. GO analysis revealed that these targets were enriched with ubiquitin protein ligase, transcription factor binding and nuclear transport. The KEGG pathways were enriched, including AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, Focal adhesion. The docking results showed that hirudin could easily dock with ITGA4, EGFR and ESR1. Conclusion: Our study demonstrates that hirudin is involved in DN therapy through a multi-targeted, multi-pathway approach. It provides a basis for further research on its mechanism of action.