Mesenchymal stem cells (MSCs) have been reported to hold promise to accelerate the wound-healing process in diabetic foot ulcer (DFU) due to the multilineage differentiation potential. Hence, this study intended to explore the wound healing role of MSC-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 phosphatase and tensin homolog (PTEN) deleted on chromosome ten. Fibroblasts in DFU samples exhibited highly expressed miR-152-3p and poorly expressed lncRNA H19 and PTEN, along with an activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt1) signaling pathway. The fibroblasts were cocultured with lncRNA H19-transfected MSCs and MSC-derived exosomes to assess the effect of the lncRNA H19/miR-152-3p/PTEN axis on the biological activities and inflammation in fibroblasts. Mouse models of DFU were developed by streptozotocin, which was injected with MSC-derived exosomes overexpressing lncRNA H19. lncRNA H19 in MSCs was transferred through exosomes to fibroblasts, the mechanism of which improved wound healing in DFU, corresponded 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 MSC-derived exosomes overexpressing lncRNA H19. Taken together, MSC-derived exosomal lncRNA H19 prevented the apoptosis and inflammation of fibroblasts by impairing miR-152-3p-mediated PTEN inhibition, leading to the stimulated wound-healing process in DFU.

据报道，由于多系分化潜能，间充质干细胞（MSC）有望加速糖尿病足溃疡（DFU）的伤口愈合过程。因此，本研究旨在探讨DFU中含有长非编码RNA（lncRNA）H19的MSC来源的外泌体的伤口愈合作用。预测lncRNA H19与microRNA-152-3p（miR-152-3p）结合，后者靶向在第10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）。DFU样品中的成纤维细胞表现出高表达的miR-152-3p和低表达的lncRNA H19和PTEN，以及活化的磷脂酰肌醇-4,5-双磷酸3激酶（PI3K）/蛋白激酶B（Akt1）信号传导途径。将成纤维细胞与lncRNA H19转染的MSC和MSC衍生的外泌体共培养，以评估lncRNA H19 / miR-152-3p / PTEN轴对成纤维细胞生物学活性和炎症的影响。DFU的小鼠模型是通过链脲佐菌素开发的，链佐菌素注射了过表达lncRNA H19的MSC衍生的外来体。MSCs中的lncRNA H19通过外泌体转移至成纤维细胞，其机制改善了DFU中的伤口愈合，与促进成纤维细胞增殖和迁移以及抑制细胞凋亡和炎症有关。注射过表达lncRNA H19的MSC来源的外来体后，DFU小鼠的伤口愈合得到了促进。综上所述，MSC衍生的外泌体lncRNA H19通过削弱miR-152-3p介导的PTEN抑制作用来预防成纤维细胞的凋亡和炎症，