The mesenchymal stem cell-derived exosomal long noncoding RNA H19 promotes wound healing in diabetic foot ulcers

Mesenchymal stem cells (MSCs) have been reported to hold promise to accelerate wound-healing process in diabetic foot ulcer (DFU) due to the multi-lineage differentiation potential. Hence, this study intended to explore the wound healing role of MSCs-derived exosomes containing long noncoding RNA (lncRNA) H19 in DFU. LncRNA H19 was predicated to bind to microRNA-152-3p (miR-152-3p), which targeted PTEN. Fibroblasts in DFU samples exhibited highly expressed miR-152-3p and poorly expressed lncRNA H19 and PTEN, along with activated PI3K/AKT signaling pathway. The fibroblasts were co-cultured with lncRNA H19-transfected MSCs and MSCs-derived exosomes to assess the effect of lncRNA H19/miR-152-3p/PTEN axis on the biological activities and inflammation in fibroblasts. Mouse models of DFU were developed by streptozotocin, which were injected with MSCs-derived exosomes overexpressing lncRNA H19. LncRNA H19 in MSCs was transferred through exosomes to fibroblasts, the mechanism of which improved wound healing in DFU, correspond to promoted fibroblast proliferation and migration as well as suppressed apoptosis and inflammation. Wound healing in mice with DFU was facilitated following the injection of MSCs-derived exosomes overexpressing lncRNA H19. Taken together, MSCs-derived exosomal lncRNA H19 prevented the apoptosis and inflammation of fibroblasts by impairing miR-152-3p-mediated PTEN inhibition, leading to stimulated the wound healing process in DFU.

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