Reconstructive and Plastic Surgery, General Hospital of Northern Theater Command, Shenyang, China.
Graduate School, Jinzhou Medical University, 40 Songpo Road, Jinzhou 121001, China.
Biomed Res Int. 2020 Dec 9;2020:8605407. doi: 10.1155/2020/8605407. eCollection 2020.
Hypertrophic scarring is a skin collagen disease that can occur following skin damage and is unlikely to heal or subside naturally. Since surgical treatment often worsens scarring, it is important to investigate the pathogenesis and prevention of hypertrophic scarring. Thrombospondin-1 (THBS1) is a matrix glycoprotein that can affect fibrosis by activating TGF-1, which plays a key role in wound repair and tissue regeneration; therefore, we investigated the effects of THBS1 on the biological function of hypertrophic scar fibroblasts. THBS1 expression was measured in hypertrophic scars and adjacent tissues as well as normal fibroblasts, normal scar fibroblasts, and hypertrophic scar fibroblasts. In addition, THBS1 was overexpressed or silenced in hypertrophic scar fibroblasts to determine the effects of THBS1 on cell proliferation, apoptosis, and migration, as well as TGF-1 expression. Finally, the role of THBS1 in hypertrophic scarring was confirmed using a mouse model. We found that THBS1 expression was increased in hypertrophic scar tissues and fibroblasts and promoted the growth and migration of hypertrophic scar fibroblasts as well as TGF-1 expression. Interestingly, we found that si-THBS1 inhibited the occurrence and development of bleomycin-induced hypertrophic scars and downregulated TGF-1 expression. Together, our findings suggest that THBS1 is abnormally expressed in hypertrophic scars and can induce the growth of hypertrophic scar fibroblasts by regulating TGF-1. Consequently, THBS1 could be an ideal target for treating hypertrophic scarring.
增生性瘢痕是一种皮肤胶原疾病，可发生于皮肤损伤后，且不易自然愈合或消退。由于手术治疗常使瘢痕恶化，因此研究增生性瘢痕的发病机制和预防措施非常重要。血小板反应蛋白-1（THBS1）是一种基质糖蛋白，可通过激活 TGF-β1 影响纤维化，后者在伤口修复和组织再生中发挥关键作用；因此，我们研究了 THBS1 对增生性瘢痕成纤维细胞生物学功能的影响。测量了增生性瘢痕及其邻近组织以及正常成纤维细胞、正常瘢痕成纤维细胞和增生性瘢痕成纤维细胞中的 THBS1 表达。此外，在增生性瘢痕成纤维细胞中过表达或沉默 THBS1，以确定 THBS1 对细胞增殖、凋亡和迁移以及 TGF-β1 表达的影响。最后，使用小鼠模型证实了 THBS1 在增生性瘢痕形成中的作用。我们发现 THBS1 在增生性瘢痕组织和成纤维细胞中表达增加，并促进了增生性瘢痕成纤维细胞的生长和迁移以及 TGF-β1 的表达。有趣的是，我们发现 si-THBS1 抑制了博来霉素诱导的增生性瘢痕的发生和发展，并下调了 TGF-β1 的表达。总之，我们的研究结果表明，THBS1 在增生性瘢痕中异常表达，可通过调节 TGF-β1 诱导增生性瘢痕成纤维细胞的生长。因此，THBS1 可能是治疗增生性瘢痕的理想靶点。
