Shared molecular mechanisms of vascular endothelial cells in psoriasis and diabetes comorbidity

Introduction
Dysfunction of vascular endothelial cells (VECs) is a common feature of both psoriasis and diabetes. Comorbidity of these two conditions increases the risk of diabetic foot ulcer (DFU), yet the shared mechanisms remain unclear.

Aim
This study aimed to systematically elucidate the shared pathological mechanisms of the two diseases from the perspective of VECs and explore their association with the pathogenesis of DFU.

Material and methods
We integrated and analysed single-cell transcriptomic data from skin samples of healthy controls, psoriasis patients, diabetes patients, and DFU patients. VECs were clustered and annotated, followed by application of differential expression analysis, weighted gene co-expression network analysis, and protein-protein interaction network analysis.

Results
VECs could be classified into five distinct subclusters. We identified 561 co-upregulated genes in VECs from both psoriasis and diabetes, and 12 core shared genes (e.g., CEBPB, ABL2) were further pinpointed, which were highly expressed in clusters A and P and showed upregulation under in vitro stimulation. Additionally, DFU and psoriasis shared upregulated genes (e.g., S100A7, KRT16), primarily enriched in subclusters A and C2, suggesting their roles in sustained inflammation and tissue remodelling.

Conclusions
This study provides an explanation for the comorbidity mechanism of psoriasis and diabetes as well as the risk of vascular complications, laying a foundation for developing cross-disease therapeutic strategies targeting VECs.