The 1st Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Osaka, Japan.
Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Health Economics and Management, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Pediatric Dentistry, Osaka Dental University, Osaka, Japan.
Peptides. 2020 Dec;134:170405. doi: 10.1016/j.peptides.2020.170405. Epub 2020 Sep 10.
Osteopontin-derived SVVYGLR (SV) 7-amino-acid sequence is a multifunctional and synthetic SV peptide implicated in angiogenesis, production of collagen III, and fibroblast differentiation into myofibroblasts. This study investigated the effect of the SV peptide on mucosal wound healing activity. Normal human-derived gingival fibroblasts (NHGF) and human oral mucosa keratinocytes (HOMK) were used for in vitro experiments. In addition, an oral punch wound was prepared at the buccal mucosa in male rats aged 11 weeks, and we evaluated the effect of local injection of SV peptide on wound healing. The synthetic SV peptide showed no influence on the proliferation and adhesion properties of NHGF and HOMK, but it enhanced the cell motility and migration activities. TGF-β1 receptor inhibitor, SB431542 or SB505124, substantially suppressed the SV peptide-induced migration activity, suggesting an involvement of TGF-β1 receptor activation. Furthermore, SV peptide accelerated the healing process of an in vivo oral wound model, compared with control groups. Further immunohistological staining of wound tissue revealed that an increase in capillary growth and the greater number of fibroblasts and myofibroblasts that migrated into the wound area might contribute to the facilitation of the healing process produced by the SV peptide. The SV peptide has beneficial effects on oral wound healing through enhancement of the earlier phase consisting of angiogenesis and remodeling with granulation tissue. The synthetic SV peptide can be a useful treatment option, particularly for intractable mucosal wounds caused by trauma or surgery for progressive lesions such as oral cancer.
骨桥蛋白衍生的 SVVYGLR（SV）7 个氨基酸序列是一种多功能的合成 SV 肽，涉及血管生成、III 型胶原产生和纤维母细胞向肌成纤维细胞分化。本研究调查了 SV 肽对黏膜伤口愈合活性的影响。使用正常人类牙龈成纤维细胞（NHGF）和人口腔黏膜角质形成细胞（HOMK）进行体外实验。此外，在 11 周龄雄性大鼠的颊黏膜上制备口腔打孔伤口，并评估 SV 肽局部注射对伤口愈合的影响。合成的 SV 肽对 NHGF 和 HOMK 的增殖和黏附特性没有影响，但增强了细胞的运动性和迁移活性。TGF-β1 受体抑制剂 SB431542 或 SB505124 显著抑制 SV 肽诱导的迁移活性，表明 TGF-β1 受体的激活参与其中。此外，SV 肽与对照组相比，加速了体内口腔伤口模型的愈合过程。对伤口组织的进一步免疫组织化学染色显示，毛细血管生长增加，以及更多迁移到伤口区域的成纤维细胞和肌成纤维细胞，可能有助于促进 SV 肽产生的愈合过程。SV 肽通过增强包括血管生成和肉芽组织重塑在内的早期阶段，对口腔伤口愈合具有有益的影响。合成的 SV 肽可以作为一种有用的治疗选择，特别是对于创伤或手术引起的难以愈合的黏膜伤口，以及口腔癌等进行性病变。
