UCMSC-derived exosomal circDLGAP4 enhances HFF-1 cell proliferation and migration by promoting ZNF217 promoter H3K27...

Umbilical cord mesenchymal stem cells (UCMSCs) have been shown to actively participate in diabetic foot ulcer (DFU) wound healing. The human foreskin fibroblast-1 (HFF-1) cell line is a crucial and widely used in vitro model for fundamental research on DFUs. In this study, the role of UCMSC-derived exosomal circDLGAP4 in high-glucose (HG)-stressed HFF-1 cells was clarified, in particular whether it regulates the TATA-box binding protein-associated factor 15 (TAF15)/p300/zinc finger protein 217 (ZNF217) axis to enhance cell proliferation and migration. We confirmed that UCMSC-derived exosomes that contained circDLGAP4 in abundance enhanced the proliferation and migration of HG-stressed HFF-1 cells. Under an HG environment, ZNF217 was downregulated in the HFF-1 cells, whereas its overexpression promoted the proliferation and migration of the cells, an effect facilitated by its own activation via the p300-mediated H3K27 acetylation of its gene promoter. The p300 mRNA was stabilized through interaction with TAF15, while the expression of TAF15 was upregulated through its interaction with circDLGAP4. Additionally, exosomal circDLGAP4 promoted wound healing in mice with DFUs. In conclusion, UCMSC-derived exosomal circDLGAP4 enhanced HFF-1 cell proliferation and migration under HG conditions in vitro and promoted diabetic wound healing in vivo by activating the TAF15/p300/ZNF217 axis.