Exosomes from adipose-derived mesenchymal stem cell improve diabetic wound healing and inhibit fibrosis via miR-128-1-5p/TGF-β1/Smad axis

Objective: Difficult -to -heal wound is a prevalent and significant complication of diabetes, characterized by impaired functionality of epithelial cells such as fibroblasts. This study aims to investigate the potential mechanism of ADSC-Exos promoting diabetic wound healing by regulating fibroblast function. Materials and methods: ADSC-Exos were confirmed through TEM, NTA, and Western Blot techniques. The study conducted on rat skin fibroblasts (RSFs) exposed to 33 mmol/L glucose in vitro. We used cck-8, EDU, transwell, and scratch assays to verify the proliferation and migration of RSFs. Furthermore, levels of TGF- 8 1 and a-SMA proteins were determined by immunofluorescence and Western Blot. RSFs were transfected with miR-128-1-5p mimics and inhibitors, followed by quantification of TGF- 8 1, a-SMA, Col I and Smad2/3 protein levels using Western Blot. In vivo, the effects of ADSC-Exos on diabetic wounds were assessed using digital imaging, histological staining, as well as Western Blot analysis. Results: In vitro, ADSC-Exos significantly enhanced proliferation and migration of RSFs while reducing the expression of TGF- 8 1 and a-SMA. In vivo, ADSC-Exos effectively promoted diabetic wound healing and mitigated scar fibrosis. Additionally, ADSC-Exos exhibited elevated levels of miR-128-1-5p, which targets TGF- 8 1, resulting in a notable reduction in TGF- 8 1, a-SMA, Col I and smad2/3 phosphorylation in RSFs. Conclusion: In conclusion, our results demonstrated that ADSC-Exos promoted diabetic wound healing, and inhibited skin fibrosis by regulating miR-128-1-5p/TGF- 8 1/Smad signaling pathway, which provides a promising innovative treatment for diabetic wound healing.