Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
J Dent Res. 2012 Aug;91(8):764-70. doi: 10.1177/0022034512451449. Epub 2012 Jun 14.
During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-β is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-β, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-β/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.
在牙周组织再生过程中，抑制牙龈向下生长对于促进间充质细胞迁移到缺损部位是必要的。转化生长因子（TGF）-β是一种多功能细胞因子，具有多种细胞功能，包括调节上皮细胞的生长。最近的研究表明，TGF-β的下游转录因子 Smad2 在上皮组织的伤口愈合中发挥着至关重要的作用。因此，我们研究了 Smad2 过表达对牙龈伤口再上皮化的影响。用角蛋白 14 启动子（k14-smad2）驱动的 Smad2 过表达转基因小鼠被证实其牙龈基底上皮中有显著的 Smad2 磷酸化。在腭牙龈上打孔，在第 7 天进行组织学评估伤口愈合情况。与野生型小鼠相比，k14-smad2 中的再上皮化在第 2 天显著延迟，而在第 7 天胶原沉积增强。此外，在 k14-smad2 中，伤口边缘角质形成细胞中角蛋白 16（K16）的表达，作为角质形成细胞迁移的指标，显著受到抑制。K16 的抑制与相应上皮中 Smad2 的诱导相吻合，而 BrdU 掺入不受影响。这些结果表明，Smad2 在调节牙龈伤口愈合过程中的角质形成细胞迁移方面具有抑制作用。TGF-β/Smad2 信号转导介导的 K16 表达改变必须在牙周组织再生过程中受到严格调控。
