Department of Plastic, Aesthetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, P. R. China.
Department of Orthopedics, Huanggang Central Hospital of Yangtze University, Huanggang, 438000, P. R. China.
Arch Dermatol Res. 2024 Jun 1;316(6):323. doi: 10.1007/s00403-024-03065-2.
Refractory diabetic wounds are still a clinical challenge that can cause persistent inflammation and delayed healing. Exosomes of adipose stem cells (ADSC-exos) are the potential strategy for wound repair; however, underlying mechanisms remain mysterious. In this study, we isolated ADSC-exos and identified their characterization. High glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) to establish in vitro model. The biological behaviors were analyzed by Transwell, wound healing, and tube formation assays. The underlying mechanisms were analyzed using quantitative real-time PCR, co-immunoprecipitation (Co-IP), IP, and western blot. The results showed that ADSC-exos promoted HG-inhibited cell migration and angiogenesis. In addition, ADSC-exos increased the levels of TRIM32 in HG-treated HUVECs, which promoted the ubiquitination of STING and downregulated STING protein levels. Rescue experiments affirmed that ADSC-exos promoted migration and angiogenesis of HG-treated HUVECs by regulating the TRIM32/STING axis. In conclusion, ADSC-exos increased the levels of TRIM32, which interacted with STING and promoted its ubiquitination, downregulating STING levels, thus promoting migration and angiogenesis of HG-treated HUVECs. The findings suggested that ADSC-exos could promote diabetic wound healing and demonstrated a new mechanism of ADSC-exos.
难治性糖尿病创面仍是临床面临的挑战，可导致持续炎症和愈合延迟。脂肪干细胞外泌体（ADSC-exos）是创面修复的潜在策略；然而，其潜在机制仍不清楚。本研究中，我们分离了 ADSC-exos 并对其特征进行了鉴定。高糖（HG）刺激人脐静脉内皮细胞（HUVEC）建立体外模型。通过 Transwell、划痕愈合和管形成实验分析细胞的生物行为。采用实时定量 PCR、共免疫沉淀（Co-IP）、免疫沉淀（IP）和 Western blot 分析潜在机制。结果表明，ADSC-exos 促进 HG 抑制的细胞迁移和血管生成。此外，ADSC-exos 增加了 HG 处理的 HUVEC 中 TRIM32 的水平，促进了 STING 的泛素化，下调了 STING 蛋白水平。挽救实验证实，ADSC-exos 通过调节 TRIM32/STING 轴促进 HG 处理的 HUVEC 的迁移和血管生成。总之，ADSC-exos 增加了 TRIM32 的水平，TRIM32 与 STING 相互作用并促进其泛素化，下调 STING 水平，从而促进 HG 处理的 HUVEC 的迁移和血管生成。研究结果表明 ADSC-exos 可促进糖尿病创面愈合，并展示了 ADSC-exos 的新机制。
