Epidermal stem cell-derived exosomes improve wound healing by promoting the proliferation and migration of human skin fibroblasts

被引:3
作者
Kang, Deni [1 ]
Wang, Xiaoxiang [2 ]
Chen, Wentao [3 ]
Mao, Lujia [4 ]
Zhang, Weiqiang [5 ]
Shi, Yan [6 ]
Xie, Julin [2 ]
Yang, Ronghua [1 ]
机构
[1] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Burn & Plast Surg, 1 Panfu Rd, Guangzhou 510180, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Burns, 58 Zhongshan Second Rd, Guangzhou 510062, Guangdong, Peoples R China
[3] Foshan Second Peoples Hosp, Dept Med cosmetol, 78 Weiguo Rd, Foshan 528000, Guangdong, Peoples R China
[4] South China Univ Technol, Guangzhou Peoples Hosp 1, Dept Burn & Plast Surg, 1 Panfu Rd, Guangzhou 510180, Guangdong, Peoples R China
[5] Guangdong Med Univ, Clin Med Coll 1, 2 Wenming East Rd, Zhanjiang 524002, Guangdong, Peoples R China
[6] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Dept Plast,Med Ctr Burn Plast & Wound Repair, 17 Yongwai Zheng St, Nanchang 330006, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Epidermal stem cells; Exosomes; Wound healing; Human skin fibroblasts; Skin regeneration; Migration; Proliferation; PROCOLLAGEN MESSENGER-RNAS; COLLAGEN GENE-EXPRESSION; THERAPY; KELOIDS;
D O I
10.1093/burnst/tkae047
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background Epidermal stem cells (ESCs) are primarily located in the basal layer of the epidermis and play a crucial role in wound healing. ESCs-derived exosomes (ESCs-Exo) are emerging as promising candidates for skin regeneration and wound healing. However, the underlying mechanisms remain unclear. This study aims to investigate the role and mechanisms of ESCs-Exo in promoting the proliferation, migration, and collagen synthesis of human skin fibroblasts (HSFBs).Methods This study generated, isolated, and characterized ESC-Exos. The effects of ESCs-Exo on the proliferation of human skin fibroblasts (HSFBs) were detected via Cell Counting Kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU), and Proliferating Cell Nuclear Antigen (PCNA) and Marker of Proliferation Ki-67 (MKI67) gene expression methods. The effect of ESCs-Exo on the migration of HSFBs was detected via a transwell assay and a scratch test. The concentrations of collagen secreted by the HSFBs and the mRNAs of the two kinds of collagen expressed by the HSFBs were analyzed. We also analyzed the phosphorylation of Protein Kinase N1 (PKN1) and the expression of cyclins via western blotting. Finally, the effect of ESCs-Exo on wound healing was verified by animal experiments, and the key genes and signaling pathways of ESCs-Exo were excavated by transcriptomic analysis.Results Western blotting revealed that the exosomes of ESCs highly expressed established markers such as Alix, CD63, and CD9. ESC-Exos significantly promoted HSFB proliferation and migration in a dose-dependent manner, as well as HSFB collagen synthesis, and effectively increased the ratio of collagen III/I. In addition, bioinformatics analysis showed that the expression of key gene C-X-C motif chemokine ligand 9 was lower in the ESCs-Exo group, which may promote wound healing by regulating PKN1-cyclin and tumor necrosis factor signaling pathways. Animal experiments demonstrated that ESCs-Exo could reduce inflammation and accelerate wound healing.Conclusions In this study, we found that ESCs-Exo may improve wound healing by promoting the proliferation and migration of HSFBs.
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页数:14
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