Inhibition of the transforming growth factor-β/Smad signaling pathway in the epithelium of oral lichen
Inhibition of the transforming growth factor-β/Smad signaling pathway in the epithelium of oral lichen
复制标题
DOI：
10.1046/j.1523-1747.2003.12633.x
复制
发表时间：
2003-12-01
影响因子：
6.5
通讯作者：
Schenck, K
中科院分区：
文献类型：
--
作者：
Karatsaidis, A;Schreurs, O;Schenck, K
与正常口腔粘膜相比，口腔苔藓的上皮基底细胞过度增殖。在这项研究中，我们研究了这是否与上皮生长抑制因子转化生长因子（TGF）β 1的破坏生产，激活或信号转导有关。原位免疫组化结果显示，正常口腔粘膜上皮细胞中Smad 4和Smad 2/3均呈胞核和胞浆磷酸化状态，Smad 7呈低表达或不表达。潜伏相关肽TGF-β 1、潜伏TGF-β结合蛋白1、TGF-β I型受体和TGF-β II型受体的表达很容易观察到，但只有非常少的TGF-β 1被激活。在红斑性口腔苔藓中，基底和下部棘上皮层显示潜伏相关肽TGF-β 1、TGF-β I型受体和TGF-β II型受体染色。在棘层和颗粒层的上层，这些分子的染色很少，但活性TGF-β 1的染色明显。与正常口腔黏膜相比，口腔黏膜糜烂性苔藓中Smad 4和磷酸化Smad 2/3染色的上皮细胞核数量明显减少。结果表明，Smad 7蛋白在口腔黏膜苔藓的基底层和基底层上细胞质中有较强的表达，而在棘层和颗粒层中，Smad 7蛋白定位于细胞膜。原位杂交结果显示，几乎所有的基底角质形成细胞中Smad 7的mRNA强表达，与此相反，没有或偶尔非常弱的Smad 7的mRNA表达被认为是在这些细胞在正常的口腔粘膜。观察结果表明，抑制TGF-β/Smad途径可能是导致口腔黏膜苔藓角质形成细胞过度增殖的原因。
The basal cells in epithelium of the erythematous form of oral lichen display hyperproliferation compared with normal oral mucosa. In this study we examined whether this is associated with disrupted production, activation, or signal transduction of the epithelial growth inhibitor transforming growth factor (TGF) beta1. In situ immunostaining showed that most epithelial cells in normal oral mucosa had nuclear and cytoplasmic Smad4 and phosphorylated Smad2/3, but expressed little or no Smad7. Expression of latency-associated peptide TGF-beta1, latent TGF-beta binding protein 1, TGF-beta type I receptor, and TGF-beta type II receptor was readily seen, but only very little TGF-beta1 was activated. In erythematous oral lichen, basal and lower spinous epithelial layers showed staining for latency-associated peptide TGF-beta1, TGF-beta type I receptor, and TGF-beta type II receptor. A band with scanty staining for these molecules, but with marked staining for active TGF-beta1, was seen in the upper spinous and granular layers. Numbers of epithelial cell nuclei with Smad4 and phosphorylated Smad2/3 staining were significantly reduced in erythematous oral lichen compared with normal oral mucosa. Basal and suprabasal cell layers in erythematous oral lichen showed strong cytoplasmic Smad7 protein staining, but in spinous and granular layers Smad7 was localized to the cell membrane. In situ hybridization showed strong Smad7 mRNA expression in almost all basal keratinocytes in erythematous oral lichen; by contrast, no or occasionally very weak Smad7 mRNA expression was seen in these cells in normal oral mucosa. The observations indicate that inhibition of the TGF-beta/Smad pathway may account for the hyperproliferation of keratinocytes in erythematous oral lichen.