MiR-21 regulating PVT1/PTEN/IL-17 axis towards the treatment of infectious diabetic wound healing by modified GO-derived biomaterial in mouse models

Abstract

Background Diabetic foot ulcer (DFU), persistent hyperglycemia and inflammation, together with impaired nutrient and oxygen deficiency, can present abnormal angiogenesis following tissue injury such that these tissues fail to heal properly. It is critical to design a new treatment method for DFU patients with a distinct biomechanism that is more effective than current treatment regimens. Method Graphene oxide (GO) was combined with a biocompatible polymer as a kind of modified GO-based hydrogel. The characterization of our biomaterial was measured in vitro. The repair efficiency of the biomaterial was evaluated in the mouse full-skin defect models. The key axis related to diabetic wound (DW) was identified and investigated using bioinformatics analyses and practical experiments. Result In the study, we found that our modified GO-based wound dressing material is a promising option for diabetic wound. Secondly, our biomaterial could enhance the secretion of small EVs (sEVs) with more miR-21 by adipose-derived mesenchymal stem cells (AD-MSCs). Thirdly, the PVT1/PTEN/IL-17 axis was found to be decreased to promote DFU wound healing by modifying miR-21 with the discovery of PVT1 as a critical LncRNA by bioinformatics analysis and tests. Conclusion These findings could aid in the development of clinical care strategies for DFU wounds.

Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma

“…Both miR-21 and miR-210 are known to be activated by hypoxic conditions. Hypoxia occurs in cancer, during wound healing, as well as in other pathological conditions [ 24 , 25 , 26 , 27 , 28 ]. Lowering miR-21 and miR-210 expression decreases cell migration and invasion of pancreatic stellate cells (PSCs) and CAFs [ 29 ].…”

IL-17 in wound repair: bridging acute and chronic responses

“…Research has shown that the improved GO-based wound dressing has the potential to increase the production of sEVs by increasing the amount of miR-21 that is produced by AD-MSCs [ 92 ]. In order to enhance wound healing in the diabetic foot (DF), it has been discovered through bioinformatics research and testing that PVT1 is the most important long noncoding RNA (lncRNA).…”

Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions

“…This loading model can stimulate cells to secrete cytokines and thus promote cell proliferation and remodeling. Chen et al 71 designed a hydrogel loaded with graphene oxide (GO). This hydrogel loaded with GO can induce sEVs secretion of miR‐21‐5p in adipose‐derived MSCs through up‐regulating the phosphoinositide‐3 kinase (PI3K)/protein kinase B (PKB/AKT) signal pathway.…”