Tsai Shawn H, Tsao Li-Pen, Chang Shih-Hsin, Ho Tsung-Chuan, Tung Kwang-Yi, Wu Ai-Ching, Tsao Yeou-Ping
Department of Ophthalmology, Mackay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.
Department of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
Exp Ther Med. 2017 Nov;14(5):4853-4861. doi: 10.3892/etm.2017.5134. Epub 2017 Sep 19.
A previous study by our group showed that a 44-amino-acid fragment of pigment epithelium-derived factor (PEDF) facilitated corneal epithelial wound healing. In the present study this fragment was shortened to obtain peptides of 18, 20 and 29 amino acids in length, and their promoting effects on the healing of full-thickness skin wounds were assessed. Peptides were delivered periodically by topical application to punch wounds of mice. The wound healing speed was evaluated by measuring the reduction of wound areas at 4 and 7 days after injury. Histological analysis with Masson's trichrome staining was used to confirm epithelialization and dermal collagen deposition. Proliferation of epithelial basal cells was documented by 5-bromo-2'-deoxyuridine incorporation. Hair follicle stem cells were identified by immunostaining for leucine-rich repeat-containing G protein-coupled receptor 6. The results indicated that the 20- and 29-amino-acid short peptides significantly reduced the time required for wound healing compared to the vehicle. Histological analysis confirmed faster epithelial cell coverage of open wounds. Treatment with the PEDF peptide fragments also contributed to granulation, tissue formation by increasing the fibroblast population and enhancing collagen deposition in the dermis. Wounds treated with PEDF peptide fragments contained more basal cells proliferated in the epithelium. Moreover, hair follicle stem cells were also stimulated to proliferate by peptide exposure. In conclusion, the present study reported the identification of two short peptides that can enhance the healing of full-thickness skin wounds following topical application. The underlying mechanisms may involve activation of basal cell proliferation and mobilization of hair follicle stem cells.
我们团队之前的一项研究表明，色素上皮衍生因子（PEDF）的一个44个氨基酸的片段促进了角膜上皮伤口愈合。在本研究中，该片段被缩短以获得长度为18、20和29个氨基酸的肽，并评估了它们对全层皮肤伤口愈合的促进作用。通过局部应用将肽定期递送至小鼠的打孔伤口。通过测量损伤后4天和7天伤口面积的减小来评估伤口愈合速度。使用Masson三色染色进行组织学分析以确认上皮形成和真皮胶原沉积。通过5-溴-2'-脱氧尿苷掺入记录上皮基底细胞的增殖。通过对富含亮氨酸重复序列的G蛋白偶联受体6进行免疫染色来鉴定毛囊干细胞。结果表明，与载体相比，20个和29个氨基酸的短肽显著缩短了伤口愈合所需的时间。组织学分析证实开放性伤口的上皮细胞覆盖更快。用PEDF肽片段治疗也有助于肉芽组织形成，通过增加成纤维细胞数量和增强真皮中的胶原沉积来促进组织形成。用PEDF肽片段治疗的伤口在上皮中有更多增殖的基底细胞。此外，肽暴露也刺激毛囊干细胞增殖。总之，本研究报告鉴定了两种短肽，局部应用后可增强全层皮肤伤口的愈合。潜在机制可能涉及基底细胞增殖的激活和毛囊干细胞的动员。
