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

• Published in: Molecular and cellular endocrinology 2024-07, Vol.588, p.112213-112213, Article 112213
• Main Authors: Liang, Qiu, Zhou, Danlian, Ge, Xiuyu, Song, Peijun, Chu, Weiwei, Xu, Jing, Shen, Yan
• Format: Article
• Language: English
• Subjects: ADSC-Exos; Diabetic wound; miR-128-1-5p; Smad pathway; TGF-β1
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2024.112213

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. 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-β1 and α-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-β1, α-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. In vitro, ADSC-Exos significantly enhanced proliferation and migration of RSFs while reducing the expression of TGF-β1 and α-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-β1, resulting in a notable reduction in TGF-β1, α-SMA, Col I and smad2/3 phosphorylation in RSFs. In conclusion, our results demonstrated that ADSC-Exos promoted diabetic wound healing, and inhibited skin fibrosis by regulating miR-128-1-5p/TGF-β1/Smad signaling pathway, which provides a promising innovative treatment for diabetic wound healing. [Display omitted] •We first verified ADSC-Exosomal miR-128-1-5p can inhibit skin fibrosis.•Our data revealed ADSC-Exos can inhibit TGF-β1 expression induced by high glucose.•ADSC-Exos can decrease α-SMA and Col I through the miR-128-1-5p/TGF-β1/Smad axis.