Genomic mapping of diabetic kidney disease biomarkers and identification of potential inhibitors through virtual screening.

Abstract

Background: Diabetic kidney disease (DKD) is a common and serious complication of diabetes mellitus, marked by a multifactorial pathogenesis and the absence of sensitive diagnostic biomarkers. Identifying novel molecular targets and therapeutic options is essential to improve early diagnosis and treatment outcomes.

Methods: To uncover potential biomarkers and therapeutic candidates, we performed an integrated genomic analysis using microarray and RNA-seq datasets from the Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA) databases. Differentially expressed genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis. Key genes were further explored through virtual screening of an FDA-approved compound library using molecular docking techniques. Drug-likeness was assessed via Lipinski's rule of five.

Results: A total of 40 DEGs were identified, among which ISCU (downregulated; involved in iron-sulfur cluster biogenesis) and AP1S2 (upregulated; associated with vesicular trafficking) emerged as potential biomarkers. PPI analysis revealed their involvement in critical DKD-related pathways, such as extracellular matrix remodeling and oxidative stress. Virtual screening identified six FDA-approved compounds with high binding affinity (≤-7.96 kcal/mol) to ISCU, notably ZINC000001576020, all of which complied with Lipinski's rule.

Conclusions: This in-silico study nominates ISCU and AP1S2 as candidate diagnostic biomarkers for DKD and identifies computationally prioritized inhibitors targeting ISCU. These findings require experimental validation but provide a molecular framework for precision diagnosis and therapeutic development. These findings offer new molecular insights that could inform precision diagnosis and personalized treatment strategies for diabetic kidney disease.