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环孢素A诱导的牙龈过度增生中上皮-间质转化标志物的免疫组织化学定位

Immunohistochemical Localization of Epithelial Mesenchymal Transition Markers in Cyclosporine A Induced Gingival Overgrowth.

作者信息

Arora Hitesh, Madapusi Balaji Thodur, Ramamurti Anjana, Narasimhan Malathi, Periasamy Soundararajan, Rao Suresh Ranga

机构信息

Post Graduate Student, Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra University , Porur, Chennai, India .

Associate Professor, Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra University , Porur, Chennai, India .

出版信息

J Clin Diagn Res. 2016 Aug;10(8):ZC48-52. doi: 10.7860/JCDR/2016/20808.8271. Epub 2016 Aug 1.

Abstract

INTRODUCTION

Cyclosporine, an immunosuppressive agent used in the management of renal transplant patients is known to produce Drug Induced Gingival Overgrowth (DIGO) as a side effect. Several mechanisms have been elucidated to understand the pathogenesis of DIGO. Recently, epithelial mesenchymal transition has been proposed as a mechanism underlying fibrosis of various organs.

AIM

The aim of the study was to investigate if Epithelial Mesenchymal Transition (EMT) operates in Cyclosporine induced gingival overgrowth.

MATERIALS AND METHODS

The study involved obtaining gingival tissue samples from healthy individuals (n=17) and subjects who exhibited cyclosporine induced gingival overgrowth (n=18). Presence and distribution of E-Cadherin, S100 A4 and alpha smooth muscle actin (α-SMA) was assessed using immunohistochemistry and cell types involved in their expression were determined. The number of α- SMA positive fibroblasts were counted in the samples.

RESULTS

In control group, there was no loss of E-Cadherin and a pronounced staining was seen in the all layers of the epithelium in all the samples analysed (100%). S100 A4 staining was noted in langerhans cells, fibroblasts, endothelial cells and endothelial lined blood capillaries in Connective Tissue (CT) of all the samples (100%) while α - SMA staining was seen only on the endothelial lined blood capillaries in all the samples (100%). However in DIGO, there was positive staining of E-Cadherin only in the basal and suprabasal layers of the epithelium in all the samples (100%). Moreover there was focal loss of E-Cadherin in the epithelium in eight out of 18 samples (44%). A break in the continuity of the basement membrane was noted in three out of 18 samples (16%) on H & E staining.

CONCLUSION

Based on the analysis of differential staining of the markers, it can be concluded that EMT could be one of the mechanistic pathways underlying the pathogenesis of DIGO.

摘要

引言

环孢素是一种用于肾移植患者管理的免疫抑制剂,已知会产生药物性牙龈增生(DIGO)作为副作用。已经阐明了几种机制来理解DIGO的发病机制。最近,上皮-间质转化被提出作为各种器官纤维化的潜在机制。

目的

本研究的目的是调查上皮-间质转化(EMT)是否在环孢素诱导的牙龈增生中起作用。

材料和方法

该研究涉及从健康个体(n = 17)和表现出环孢素诱导的牙龈增生的受试者(n = 18)中获取牙龈组织样本。使用免疫组织化学评估E-钙黏蛋白、S100 A4和α平滑肌肌动蛋白(α-SMA)的存在和分布,并确定参与其表达的细胞类型。对样本中α-SMA阳性成纤维细胞的数量进行计数。

结果

在对照组中,E-钙黏蛋白没有丢失,在所有分析的样本(100%)的上皮各层中均可见明显染色。在所有样本(100%)的结缔组织(CT)中的朗格汉斯细胞、成纤维细胞、内皮细胞和内皮衬里的毛细血管中均观察到S100 A4染色,而在所有样本(100%)中仅在内皮衬里的毛细血管上观察到α-SMA染色。然而,在DIGO中,所有样本(100%)中E-钙黏蛋白仅在上皮的基底层和基底上层呈阳性染色。此外,18个样本中有8个(44%)的上皮中E-钙黏蛋白有局灶性丢失。在苏木精和伊红染色的18个样本中有3个(16%)注意到基底膜连续性中断。

结论

基于对标志物差异染色的分析,可以得出结论,EMT可能是DIGO发病机制的机制途径之一。

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Loss of basement membrane integrity in human gingival overgrowth.人类牙龈增生中基底膜完整性的丧失。
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本文引用的文献

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Elevated levels of cyclooxygenase 1 and 2 in human cyclosporine induced gingival overgrowth.人环孢素诱导的牙龈过度增生中环氧化酶1和2水平升高。
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