Altered expression of epithelial cell surface glycoconjugates and intermediate filaments at the margins of mucosal wounds

Altered expression of epithelial cell surface glycoconjugates and intermediate filaments at the margins of mucosal wounds
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DOI:
10.1046/j.1523-1747.1998.00346.x
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发表时间:
1998-10-01
影响因子:
6.5
通讯作者:
Mackenzie, I
Mackenzie, I
中科院分区:
医学1区
文献类型:
--
作者:
Dabelsteen, E;Gron, B;Mackenzie, I

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细胞间黏附的改变是必要的,以使与上皮伤口愈合和恶性侵袭相关的细胞运动类型成为可能。一些转化细胞的研究表明,上皮细胞的运动与细胞表面碳水化合物结构表达的变化有关,这些碳水化合物结构以ABO血型抗原,特别是Lewis抗原及其生物合成前体为代表。为了进一步研究细胞表面碳水化合物与角化细胞运动之间的关系,我们在人口腔黏膜上建立了实验伤口,并通过免疫组织化学方法检测了选择的细胞角蛋白(K5、K16、K19)、基膜成分(层粘连蛋白α 5和γ 2链、BP180、胶原IV和胶原VII)、血抗原前体结构Le(x)、唾液酰基-Le(x)、Le(y)、H抗原、n -乙酰乳胺和唾液酰基- t抗原的表达。损伤引起的胶原IV、层粘连蛋白γ - 2链(层粘连蛋白-5)和层粘连蛋白α -5链的表达变化与皮肤伤口相似,并用于确定上皮运动区域。研究发现,该区域Lewis抗原Y (Le(Y))和H血型抗原的染色均明显增加,Le(x)的染色减少,从而表明损伤上皮中负责H抗原合成的聚焦转移酶的表达上调。碳水化合物的表达变化从伤口边缘延伸到非损伤上皮,这种表达模式与K16相似,在外植体和邻近的非损伤上皮中也强烈上调。这些发现进一步支持了这种碳水化合物结构对上皮细胞迁移行为的影响。
Alterations in cell to cell adhesion are necessary to enable the type of cell movements that are associated with epithelial wound healing and malignant invasion. Several studies of transformed cells have related epithelial cell movement to changes in the cell surface expression of the carbohydrate structures represented by the ABO blood group antigens and, in particular, by Lewis antigens and their biosynthetic precursors. To study further the relationship between cell surface carbohydrates and keratinocyte cell movement, experimental wounds were created in human oral mucosa and examined by immunohistochemical methods for their expression of selected cytokeratins (K5, K16, K19), basement membrane components (laminin alpha 5 and gamma 2-chains, BP180, collagen IV and collagen VII), and blood group antigen precursor structures Le(x), sialosyl-Le(x), Le(y), H antigen, N-acetyllactosamine, and sialosyl-T antigen. The changes induced by wounding in the expression of collagen IV, laminin gamma 2-chain (laminin-5), and laminin alpha 5-chain were similar to those found in skin wounds and served to define the region of epithelial movement. This region was found to show a marked increase in staining for both Lewis antigen Y (Le(y)) and H blood group antigen, and decreased staining of Le(x), thus indicating an upregulation in wounded epithelium of the fucosyltransferases responsible for the synthesis of the H antigen. The changes in carbohydrate expression extended beyond the wound margin into the nonwounded epithelium, a pattern of expression similar to K16, which was also strongly upregulated in both the outgrowth and the adjacent non-wounded epithelium. These findings provide further support for an influence of such carbohydrate structures on the migratory behavior of epithelial cells.