Diabetic foot ulcer (DFU) is a destructive complication of diabetes. Negative pressure wound therapy (NPWT) promotes DFU wound healing through an undetermined mechanism. In the present study, RNA sequencing was performed on wound granulation tissue from 3 patients with DFU before and after 1 week of NPWT. The fused in sarcoma (FUS) and interleukin enhancer binding factor 2 (ILF2) encoding RNA‑binding proteins (RBPs) were screened from the sequencing data, and wound tissue samples from 24 patients with DFU were validated and analyzed before and after receiving NPWT by reverse transcription‑quantitative PCR, western blotting and immunohistochemistry. In addition, in vitro and in vivo experiments were conducted to determine the effect of the expression of FUS and ILF2 on the function of human epidermal keratinocyte cells (HaCaT cells) and the healing of diabetic skin wounds. The results indicated that NPWT induced the upregulation of 101 genes and the downregulation of 98 genes in DFU wound granulation tissue. After NPWT, the expression of FUS and ILF2 was significantly upregulated (P<0.05). Pearson's correlation coefficient showed that the changes in FUS and ILF2 before and after NPWT were negatively correlated with changes in white blood cells, the neutrophil percentage, C‑reactive protein, tumor necrosis factor‑α, reactive oxygen species, lipid peroxides, matrix metalloproteinase (MMP) 2 and MMP9 (P<0.05), but positively correlated with the anti‑inflammatory factor, IL‑4 (P<0.01). There was also a positive correlation (P<0.05) with the 4‑week ulcer healing rate. Additionally, the knockdown of FUS and ILF2 expression inhibited the proliferation and migration of HaCaT cells, while increasing cell apoptosis. In vivo, the knockdown of FUS and ILF2 significantly reduced the rate of skin wound healing in diabetic mice. The results of the present study therefore provide new insights into the mechanism by which NPWT promotes DFU wound healing. In conclusion, the RBPs, FUS and ILF2, promoted DFU wound healing by regulating the function of keratinocytes and reducing the inflammatory response and oxidative stress.
Keywords: FUS; ILF2; RNA sequencing; RNA‑binding protein; diabetic foot ulcer; keratinocyte; negative pressure wound therapy; wound healing.