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病理状态下人类牙龈中细胞角蛋白表达模式的广泛变化。

Extensive changes in cytokeratin expression patterns in pathologically affected human gingiva.

作者信息

Bosch F X, Ouhayoun J P, Bader B L, Collin C, Grund C, Lee I, Franke W W

机构信息

Institute of Cell and Tumor Biology, German Cancer Research Center, Heidelberg.

出版信息

Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;58(1):59-77. doi: 10.1007/BF02890059.

DOI:10.1007/BF02890059
PMID:2480686
Abstract

The stratified squamous epithelium of the oral gingiva and the hard palate is characterized by a tissue architecture and a cytoskeletal composition similar to, although not identical with, that of the epidermis and fundamentally different from that of the adjacent non-masticatory oral mucosa. Using immunocytochemistry with antibodies specific for individual cytokeratins, in situ hybridization and Northern blots of RNA with riboprobes specific for individual cytokeratin mRNAs, and gel electrophoresis of cytoskeletal proteins of microdissected biopsy tissue samples, we show changes in the pattern of expression of cytokeratins and their corresponding mRNAs in pathologically altered oral gingiva. Besides a frequently, although not consistently, observed increase in the number of cells producing cytokeratins 4 and 13 (which are normally found as abundant components in the sulcular epithelium and the alveolar mucosa but not in the oral gingiva) and a reduction in the number of cells producing cytokeratins 1, 10 and 11, the most extensive change was noted for cytokeratin 19, a frequent cytokeratin in diverse one-layered and complex epithelia. While in normal oral gingiva cytokeratin 19 is restricted to certain, sparsely scattered cells of --or near--the basal cell layer, probably neuroendocrine (Merkel) cells, in altered tissue of inflamed samples it can appear in larger regions of the basal cell layer(s) and, in apparently more advanced stages, also in a variable number of suprabasal cells. Specifically, our in situ hybridization experiments show that this altered suprabasal cytokeratin 19 expression is more extended at the mRNA than at the protein level, indicating that cytokeratin 19 mRNA synthesis may be a relatively early event during the alteration. These changes in cytokeratin expression under an external pathological influence are discussed in relation to other factors known to contribute to the expression of certain cytokeratins and with respect to changes occurring during dysplasia and malignant transformation of oral epithelia.

摘要

口腔牙龈和硬腭的复层鳞状上皮,其组织结构和细胞骨架组成与表皮相似但不完全相同,且与相邻的非咀嚼性口腔黏膜有根本差异。我们运用针对单个细胞角蛋白的抗体进行免疫细胞化学分析、用针对单个细胞角蛋白mRNA的核糖探针进行原位杂交和RNA的Northern印迹分析,以及对显微切割活检组织样本的细胞骨架蛋白进行凝胶电泳,来展示病理改变的口腔牙龈中细胞角蛋白及其相应mRNA表达模式的变化。除了经常(但并非始终)观察到产生细胞角蛋白4和13的细胞数量增加(这两种蛋白通常在龈沟上皮和牙槽黏膜中大量存在,但不在口腔牙龈中)以及产生细胞角蛋白1、10和11的细胞数量减少外,细胞角蛋白19的变化最为显著,它是多种单层和复层上皮中常见的细胞角蛋白。在正常口腔牙龈中,细胞角蛋白19局限于基底细胞层或其附近某些稀疏分布的细胞,可能是神经内分泌(默克尔)细胞,而在炎症样本的病变组织中,它可出现在基底细胞层的更大区域,并且在明显更晚期阶段,也出现在数量不等的基底上层细胞中。具体而言,我们的原位杂交实验表明,这种基底上层细胞角蛋白19表达的改变在mRNA水平比在蛋白质水平更广泛,这表明细胞角蛋白19 mRNA合成可能是病变过程中相对较早发生的事件。我们结合已知有助于某些细胞角蛋白表达的其他因素以及口腔上皮发育异常和恶性转化过程中发生的变化,讨论了外部病理影响下细胞角蛋白表达的这些变化。

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