University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Tokyo 113-0033, Japan.
Biochem Biophys Res Commun. 2012 Oct 19;427(2):273-9. doi: 10.1016/j.bbrc.2012.09.037. Epub 2012 Sep 16.
Re-epithelialization is an essential step of wound healing involving three overlapping keratinocyte functions: migration, proliferation and differentiation. While quorum sensing (QS) is a cell density-dependent signaling system that enables bacteria to regulate the expression of certain genes, the QS molecule N-(3-oxododecanoyl) homoserine lactone (AHL) exerts effects also on mammalian cells in a process called inter-kingdom signaling. Recent studies have shown that AHL improves epithelialization in in vivo wound healing models but detailed understanding of the molecular and cellular mechanisms are needed. The present study focused on the AHL as a candidate reagent to improve wound healing through direct modulation of keratinocyte's activity in the re-epithelialization process. Results indicated that AHL enhances the keratinocyte's ability to migrate in an in vitro scratch wound healing model probably due to the high Mmp13 gene expression analysis after AHL treatment that was revealed by real-time RT-PCR. Inhibition of activator protein 1 (AP-1) signaling pathway completely prevented the migration of keratinocytes, and also resulted in a diminished Mmp13 gene expression, suggesting that AP-1 might be essential in the AHL-induced migration. Taken together, these results imply that AHL is a promising candidate molecule to improve re-epithelialization through the induction of migration of keratinocytes. Further investigation is needed to clarify the mechanism of action and molecular pathway of AHL on the keratinocyte migration process.
再上皮化是伤口愈合的一个重要步骤，涉及到三个重叠的角质形成细胞功能：迁移、增殖和分化。虽然群体感应（QS）是一种细胞密度依赖性的信号系统，使细菌能够调节某些基因的表达，但 QS 分子 N-（3-氧代十二酰）高丝氨酸内酯（AHL）在称为种间信号传递的过程中也对哺乳动物细胞产生影响。最近的研究表明，AHL 可改善体内伤口愈合模型中的上皮化，但需要详细了解分子和细胞机制。本研究集中于 AHL 作为候选试剂，通过直接调节再上皮化过程中的角质形成细胞活性来改善伤口愈合。结果表明，AHL 增强了角质形成细胞在体外划痕愈合模型中的迁移能力，这可能是由于 AHL 处理后实时 RT-PCR 分析显示的高 Mmp13 基因表达所致。激活蛋白 1（AP-1）信号通路的抑制完全阻止了角质形成细胞的迁移，并且还导致 Mmp13 基因表达减少，表明 AP-1 可能是 AHL 诱导迁移所必需的。综上所述，这些结果表明，AHL 是一种有前途的候选分子，可通过诱导角质形成细胞迁移来改善再上皮化。需要进一步研究以阐明 AHL 对角质形成细胞迁移过程的作用机制和分子途径。
