表皮干细胞衍生的外泌体通过下调转化生长因子-β1 促进伤口愈合中的皮肤再生。
Epidermal stem cell-derived exosomes promote skin regeneration by downregulating transforming growth factor-β1 in wound healing.
机构信息
Department of Prosthodontics, Hospital of Stomatology, Jilin University, 1500 Qinghua Rd., Changchun, 130021, Jilin, China.
Jilin Provincial Laboratory of Biomedical Engineering, Jilin University, 1500 Qinghua Rd., Changchun, 130021, Jilin, China.
出版信息
Stem Cell Res Ther. 2020 Oct 23;11(1):452. doi: 10.1186/s13287-020-01971-6.
BACKGROUND
Scar formation, which may be caused by myofibroblast aggregations, is the greatest challenge during skin wound healing in the clinical setting. Studies have indicated that epidermal stem cells (EPSC) improve wound healing and reduce scar formation.
METHODS
We investigated the therapeutic effects of EPSC-derived exosomes (EPSC-Exos) on skin wound healing in a skin-defect rat model. We also examined the roles of EPSC-Exos-specific microRNAs in inhibiting the differentiation of human dermal fibroblasts (HDF) into myofibroblasts.
RESULTS
We found that EPSC-Exos increased the wound healing rate and reduced scar formation in rats. Also, EPSC-Exos improved the regeneration levels of skin appendages, nerves and vessels, as well as the natural distribution of collagen. Furthermore, we found these functions may be achieved by inhibiting the activity of transforming growth factor-β1 (TGF-β1) and its downstream genes. The results showed that some specific microRNAs, including miR-16, let-7a, miR-425-5p and miR-142-3p, were enriched in EPSC-Exos. EPSC-Exos-specific microRNAs, especially miR-425-5p and miR-142-3p, played vital roles in inhibiting myofibroblast differentiation via reducing the TGF-β1 expression in dermal fibroblasts.
CONCLUSION
We found a novel function of EPSC-Exos-specific microRNAs, suggesting that EPSC-Exos might represent a strategy to prevent scar formation during wound healing in the clinical setting.
背景
成纤维细胞聚集导致的瘢痕形成是临床皮肤伤口愈合中最大的挑战。研究表明，表皮干细胞（EPSC）可改善伤口愈合，减少瘢痕形成。
方法
我们在皮肤缺损大鼠模型中研究了 EPSC 衍生的外泌体（EPSC-Exos）对皮肤伤口愈合的治疗作用。我们还研究了 EPSC-Exos 特异性 microRNAs 在抑制人真皮成纤维细胞（HDF）分化为肌成纤维细胞中的作用。
结果
我们发现 EPSC-Exos 可提高大鼠伤口愈合率，减少瘢痕形成。此外，EPSC-Exos 可改善皮肤附属物、神经和血管的再生水平，以及胶原的自然分布。进一步研究发现，这些功能可能是通过抑制转化生长因子-β1（TGF-β1）及其下游基因的活性来实现的。结果表明，一些特异性 microRNAs，包括 miR-16、let-7a、miR-425-5p 和 miR-142-3p，在内泌体中富集。EPSC-Exos 特异性 microRNAs，特别是 miR-425-5p 和 miR-142-3p，通过降低真皮成纤维细胞中 TGF-β1 的表达，在抑制肌成纤维细胞分化方面发挥重要作用。
结论
我们发现了 EPSC-Exos 特异性 microRNAs 的新功能，提示 EPSC-Exos 可能代表了一种预防临床伤口愈合过程中瘢痕形成的策略。
Zotero 插件