Decoding Diabetes: Hub Genes as Pivotal Players in Cardiomyopathy and Kidney Disease

Diabetes mellitus (DM) induces systemic vascular dysfunction and leads to life-threatening complications, including diabetic cardiomyopathy (DCM) and diabetic kidney disease (DKD), whose shared mechanisms remain elusive. In this study, we performed an indepth bioinformatics analysis to identify shared therapeutic targets and key molecular players in DKD and DCM.

Integrated computational and experimental approaches were employed. Bioinformatics analysis of GEO datasets (GSE30122 and GSE197850) identified differentially expressed genes (DEGs). Hub genes were extracted via protein-protein interaction networks and functional enrichment. In vitro validation was performed using AGE-stimulated cardiomyocytes and podocytes analyzed by qPCR, complemented by in vivo studies in rat models. Additionally, protein-chemical interactions and drug repurposing analyses were performed.

We identified 48 common DEGs (p-adj< 0.05 and |log₂FC| > 1.0) and prioritized 7 hub genes (CD200, CRHBP, DHRS3, EMCN, HPGD, PDGFRB, and SULF1), which were validated as dysregulated in in vitro and in vivo models. Computational screening revealed 10 promising therapeutic candidates (p-adj < 0.05) targeting core pathogenic networks.

Our study is one of the first to simultaneously investigate the molecular underpinnings of DKD and DCM by integrating bioinformatics data with experimental validation. Meanwhile, the relatively small sample sizes may limit the statistical power and generalizability of the identified DEGs.

This study uncovers novel shared mechanisms between DCM and DKD, providing a framework for dual-organ protective therapies to advance the management of diabetic complications.