2-benzazepine derivative promotes skin epithelial cell migration and wound healing

为了寻找2-苯氮平衍生物的生物活性，我们发现其中一种2-苯氮平衍生物（化合物A）促进了人角化细胞来源细胞系（HaCat细胞）的细胞迁移和小鼠皮肤伤口愈合。本研究利用HaCaT细胞体外伤口愈合实验（划痕实验）评估了2-苯氮平衍生物的结构-功能关系。在N-2位置的侧链对2-苯氮卓衍生物的生物活性是重要的。在N-2侧链上，甲基与乙基之间的空间尺寸是最佳的，而在N-2侧链上，烷基链比丙基长，影响了生物活性。在划痕实验中，化合物A诱导的迁移被抗转化生长因子-β (TGF-β)的中和抗体阻断，而抗EGF的中和抗体没有作用。这些结果表明，化合物A促进上皮迁移，增加TGF-β的释放。

In search of biological activity of 2-benzazepine derivatives, we found that one of 2-benzazepine derivatives (compound A) promoted cell migration of human keratinocyte-derived cell line (HaCat cells) and wound healing of the skin in mouse. Here a structure-function relationship of 2-benzazepine derivatives was evaluated using in vitro wound healing assay (scratch assay) with HaCaT cells. A side chain at N-2 position was important for this biological activity of 2-benzazepine derivatives. The steric size between methyl and ethyl seems optimal at this side chain position, and longer alkyl chain than propyl group at N-2 position spoiled the biological activity. In the scratch assay, compound A -induced migration was blocked by the neutralizing antibody against transforming growth factor-beta (TGF-β), while neutralizing antibody against EGF had no effect. Those results indicate that compound A promotes the epithelial migration increasing the release of TGF-β.