CXCL1 promotes diabetic foot ulcer through activation of the TNF-α signaling pathway

Diabetic foot ulcer (DFU) is an immune disease associated with diabetes. C-X-C ligand 1 (CXCL1) is a pro-inflammatory factor. Both of them have been reported to associated with the activation of oxidative stress and inflammation. This study aimed to explore the relationship between CXCL1 action mechanism and DFU occurrence through studying inflammation and oxidative stress. Firstly, used bioinformatics analysis to investigate highly expressed genes/pathways in DFU based on GEO database. After that, CXCL1-specific shRNA (sh-CXCL1) was transfected in to human umbilical vein epithelial cells (HUVEC) in high glucose (HG) condition to establish sh-CXCL1 cells, then CXCL1 expression, cell viability, inflammatory levels and oxidative stress were verified. Moreover, TNF-α overexpression plasmids (oe-TNF-α) were transfected to the HG + sh-CXCL1 group cells, and TNF-α expression, cell viability, inflammatory levels and oxidative stress were also assessed. Bioinformatics analysis indicated that CXCL1 and TNF-α were highly expressed in DFU, and there was a positive correlation between them. After transfection with sh-CXCL1, in HG conditions, the expression levels of CXCL1 and TNF-α in human umbilical vein endothelial cells (HUVEC) were significantly decreased, and oxidative stress and inflammatory responses were inhibited, while cell viability was significantly increased. However, after transfection of oe-TNF-α in sh-CXCL1 cells, all these effects were reversed. CXCL1 activates the TNF-α signaling pathway, increase oxidative stress and inflammatory response, thereby inducing DFU occurrence.

The online version contains supplementary material available at 10.1007/s10616-025-00821-8.