SPRY2 mediates fibroblast dysfunction and impaired wound healing in diabetic foot ulcers by blocking the Ras/MAPK axis.

BACKGROUND: Diabetic foot ulcer (DFU) is a serious complication of diabetes, characterized by persistent inflammation and impaired wound healing. Sprouty2 (SPRY2) is a negative regulatory factor of the receptor tyrosine kinase signaling pathway and plays an important role in cell proliferation, migration and differentiation. However, the function of SPRY2 in diabetic wound healing remains unclear. This study aims to explore the regulatory role and mechanism of SPRY2 in diabetic wound healing. METHOD: This study collected skin tissues from patients with DFU to assess the expression of SPRY2. In Sprague-Dawley rats, the DFU model was established using streptozotocin, and the sh-SPRY2 lentivirus was injected into the wound site. In vitro, the fibroblasts were treated with 25 mM high glucose. Histology, immunofluorescence, Real-time fluorescence quantitative PCR detection, Western blot, EDU, Wound healing and Transwell assay were employed. RESULT: The results showed that the expression of SPRY2 was significantly upregulated in the wound tissues of DFU patients. The study found that SPRY2 could inhibit the proliferation and migration of fibroblasts and hinder the wound healing of DFU rats. Furthermore, after knocking down the expression of SPRY2, the proliferation and migration abilities of fibroblasts significantly increased, thereby promoting wound healing in DFU rats. Further studies on its potential mechanism indicated that SPRY2 inhibited the Ras/MAPK pathway, leading to dysfunction of DFU fibroblasts and difficulty in wound healing. CONCLUSION: In DFU, SPRY2 inhibits the Ras/MAPK pathway to prevent wound healing. This mechanism provides a theoretical basis for targeting SPRY2 to treat wound healing disorders.