Objective: Diabetes foot ulcer (DFU) is a serious complication of diabetes, which can lead to significant mortality and amputation rate. Our previous study found circ_072697 was highly expressed in DFU tissues, but the regulatory mechanism of circ_072697 in DFU remains unclear. Methods: The relative expressions of circ_072697, miR-3150a-3p, and KDM2A in DFU patients or advanced glycation end products (AGEs)-treated HaCaT cells (used as DFU cell model) were determined by using qRT-PCR. Cell proliferation and migration abilities were determined by using CCK-8 and Transwell assays. The interaction between miR-3150a-3p with circ_072697 or KDM2A were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Furthermore, the protein expression of genes involved in MAPK signaling pathway was detected by western blot. Results: The expression of circ_072697 was significantly upregulated in DFU tissues, while the expression of miR-3150a-3p was downregulated. Circ_072697 knockdown promoted the proliferation and migration of AGEs-treated HaCaT cells. miR-3150a-3p was confirmed as a target of circ_072697 and its inhibitor reversed the promotion effects of circ_072697 knockdown on biological behavior of cells. In addition, KDM2A was considered as a target of miR-3150a-3p and it was highly expressed in DFU samples. Importantly, circ_072697 could regulate KDM2A expression through sponging miR-3150a-3p, and this axis had effect on the MAPK signaling pathway. Conclusions: Overall, circ_072697 regulated the biological behaviors of keratinocytes in DFU via miR-3150a-3p/KDM2A axis and MAPK signaling pathway, revealing a new insight into the pathogenesis and potential therapeutic targets of DFU.

Bacterial colonisation in hypertrophic scars (HSs) has been reported, yet the precise mechanism of their contribution to scar formation remains elusive. To address this, we examined HS and normal skin (NS) tissues through Gram staining and immunofluorescence. We co‐cultured fibroblasts with heat‐inactivated Staphylococcus aureus (S. aureus) and evaluated their levels of apoptosis and proliferation by flow cytometry and Cell Counting Kit‐8 assay, respectively. Additionally, we performed proteomic analysis and western blotting to identify upregulated proteins. To assess autophagy levels, we examined light chain 3 (LC3) expression through western blotting and immunofluorescence, and transmission electron microscopy (TEM) was performed to detect autophagy‐associated vesicles. Our results demonstrated a notable increase in bacterial load, primarily S. aureus, in HS tissues. Furthermore, S. aureus promoted fibroblast proliferation and enhanced the expression of profibrotic markers such as transforming growth factor β1 (TGF‐β1), vascular endothelial growth factor (VEGF), collagen I, collagen III and α smooth muscle actin (α‐SMA). Proteomic analysis highlighted heat shock factor‐binding protein 1 (HSBP1) as a key upregulated protein mediating the profibrotic effects induced by S. aureus. Knockdown of HSBP1 reversed these effects. Intriguingly, HSBP1 also upregulated LC3 and Beclin‐1 expression and increased the number of autophagosomes in fibroblasts. Finally, when fibroblasts stimulated by S. aureus were treated with HSBP1 siRNA, autophagy levels decreased significantly. Collectively, our findings suggest that S. aureus, via HSBP1, stimulates fibroblast proliferation and promotes their transition into myofibroblasts, triggering autophagy and fibrosis. These results underscore the potential of HSBP1 as a therapeutic target for the management of HSs.