To investigate the effect of C-X-C motif chemokine ligand 11 (CXCL11) secreted by fibroblasts in high glucose environment on the migration of human umbilical vein endothelial cells (HUVECs) and the potential mechanisms.

The wound edge skin tissue of a diabetic foot ulcer （DFU） patient admitted to the Department of Wound Repair of Liyuan Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in August 2021， and an acute foot injury patient treated in the Hand Surgery Department of the same hospital in September 2021 was collected. The single-cell transcriptome sequencing was performed to analyze the interaction between chemokine ligands of fibroblasts subgroup and chemokine receptors of vascular endothelial cells subgroup. Paraffin-embedded tissue samples were collected from DFU patients （n=3） in the Department of Endocrinology and acute foot injury patients （n=3） in the Burns Department at Wuhan Third Hospital between January 2022 and December 2024. Immunohistochemistry staining was used to observe the expression of CXCL11 and C-X-C motif chemokine receptor 7 （CXCR7） in the wound edge skin tissue. Normal human foreskin fibroblasts （HFF-1） and HFF-1 treated with D-glucose were divided into normal group and high glucose group， respectively. After 48 h of culture， the supernatants from normal group and high glucose group were collected as normal fibroblasts-conditioned medium （NFs-CM） and glucose-treated fibroblasts-conditioned medium （GFs-CM）， respectively. The mRNA expression levels of CXCL11 in the cells of normal group and high glucose group were detected by real-time fluorescence quantitative polymerase chain reaction（RT-qPCR）. HUVECs were divided into complete medium group （CPM group）， NFs-CM group， and GFs-CM group， the scratch test was performed to calculate the cell migration rates at 12， 24， and 36 h after scratching. Western blot was employed to detect the expression levels of CXCR7 protein in HUVECs from CPM group， NFs-CM group， and GFs-CM group， treated for 36 h. After treatment with a neutralizing antibody against CXCL11， the experiment was divided into six groups： CPM group， CPM+anti-CXCL11 group， NFs-CM group， NFs-CM+anti-CXCL11 group， GFs-CM group， and GFs-CM+anti-CXCL11 group. Scratch tests were repeated in each group. All experiments were repeated three times. One-way ANOVA，Tukey's test and t-test were used for statistical analysis.

Compared with the wound edge skin tissue of acute foot injury， the interaction between the chemokine ligand CXCL11 of the fibroblasts subgroup and the chemokine receptor CXCR7 of the vascular endothelial cells subgroup was significantly enhanced in the wound edge skin tissue of DFU， and the expression levels of CXCL11 and CXCR7 protein in tissue from DFU were notably higher （t=25.870， 18.150； P<0.001）. Compared with normal group， the mRNA expression level of CXCL11 in HFF-1 from high glucose group was significantly elevated （t=8.412，P=0.001）. At 36 h after scratching， the migration rate of HUVECs in GFs-CM group was significantly lower than that in CPM group and NFs-CM group （P<0.001）. Western blot analysis demonstrated that CXCR7 protein expression was significantly higher in GFs-CM group than that in CPM group and NFs-CM group （P<0.001）. At 12， 24， and 36 h after scratching，compared with GFs-CM group， the migration of HUVECs was significantly enhanced in GFs-CM+anti-CXCL11 group （P<0.001）.

High glucose promotes the secretion of CXCL11 by HFF-1， and the stimulation of its cell culture supernatant can inhibit HUVECs migration and upregulate CXCR7 protein expression. Exogenous CXCL11 neutralizing antibody can enhance the migration capacity of HUVECs.