Extracellular matrix remodeling in oral submucous fibrosis:: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

Extracellular matrix remodeling in oral submucous fibrosis:: its stage-specific modes revealed by immunohistochemistry and in situ hybridization
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DOI:
10.1111/j.1600-0714.2005.00339.x
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发表时间:
2005-09-01
影响因子:
3.3
通讯作者:
Saku, T
Saku, T
中科院分区:
医学3区
文献类型:
--
作者:
Utsunomiya, H;Tilakaratne, WM;Saku, T

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背景:口腔粘膜下纤维性变(OSF)是一种与咀嚼习惯有关的口腔黏膜癌前状态,主要影响南亚人。它的组织病理学特征是上皮下结缔组织的上皮萎缩和纤维化。纤维化一直延伸到肌肉层,导致张口困难。方法:采用组织化学、免疫组织化学和原位杂交方法检测40例OSF和10例正常口腔黏膜组织中8种ECM分子的表达/沉积模式。结果:OSF早期固有层和粘膜下层均有明显的Tenascin、Perlecan、FN、III型胶原表达增强。中期,上述ECM分子和弹性蛋白在肌纤维周围广泛而不规则地沉积。晚期,这种ECM沉积减少,完全被I型胶原取代。它们的基因表达水平随着纤维化的进展而变化,但在黏膜下纤维化区的成纤维细胞中有表达。结论:OSF中ECM重塑的步骤与正常肉芽组织形成的各个阶段相似。张口受限可能是各种ECM分子丢失的结果,包括弹性蛋白在内的同质I型胶原取代了肌肉纤维。
BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown.METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization.RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas.CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.