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感染与E-钙黏蛋白启动子甲基化、E-钙黏蛋白表达下调以及纤连蛋白和α-平滑肌肌动蛋白表达增加相关——对上皮-间质转化的影响

Infection Is Associated with E-Cadherin Promoter Methylation, Downregulation of E-Cadherin Expression, and Increased Expression of Fibronectin and α-SMA-Implications for Epithelial-Mesenchymal Transition.

作者信息

Rajić Jovana, Inic-Kanada Aleksandra, Stein Elisabeth, Dinić Svetlana, Schuerer Nadine, Uskoković Aleksandra, Ghasemian Ehsan, Mihailović Mirjana, Vidaković Melita, Grdović Nevena, Barisani-Asenbauer Talin

机构信息

Department of Molecular Biology, Institute for Biological Research "Siniša Stanković", University of BelgradeBelgrade, Serbia.

OCUVAC - Center of Ocular Inflammation and Infection, Laura Bassi Centres of Expertise; Center for Pathophysiology, Infectiology and Immunology; Medical University of ViennaVienna, Austria.

出版信息

Front Cell Infect Microbiol. 2017 Jun 14;7:253. doi: 10.3389/fcimb.2017.00253. eCollection 2017.

DOI:10.3389/fcimb.2017.00253
PMID:28660176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5469886/
Abstract

() can induce scarring disease of the ocular mucosa, known as trachoma, the most common infectious cause of blindness worldwide. We hypothesized that epithelial-mesenchymal transition (EMT) contributes to the fibrotic process in trachomatous scarring. Infection of human conjunctival epithelial cells (HCjE) with activated signaling pathways involved in EMT induction, which was correlated with decreased expression of E-cadherin, guardian of the epithelial phenotype. In addition, infection was associated with increased expression of two mesenchymal cell markers: fibronectin and α-SMA. The DNA methylation statuses of selected regions of E-cadherin, fibronectin, and α-SMA genes revealed that infection was accompanied with changes in DNA methylation of the E-cadherin promoter, while the expression of the two mesenchymal markers was not related with this epigenetic event. Our data suggest that infection of conjunctival epithelial cells induces EMT-like changes that go along with modification of the methylation profile of the E-cadherin promoter and could, as one of the earliest events, contribute to processes triggering conjunctival scarring.

摘要

(某病原体)可诱发眼黏膜瘢痕形成疾病,即沙眼,它是全球最常见的感染性致盲原因。我们推测上皮-间质转化(EMT)促成了沙眼瘢痕形成中的纤维化过程。用(某病原体)感染人结膜上皮细胞(HCjE)会激活参与诱导EMT的信号通路,这与上皮表型守护者E-钙黏蛋白表达降低相关。此外,(某病原体)感染与两种间充质细胞标志物(纤连蛋白和α-平滑肌肌动蛋白)表达增加有关。E-钙黏蛋白、纤连蛋白和α-平滑肌肌动蛋白基因选定区域的DNA甲基化状态显示,(某病原体)感染伴随着E-钙黏蛋白启动子DNA甲基化的变化,而两种间充质标志物的表达与这一表观遗传事件无关。我们的数据表明,结膜上皮细胞感染会诱导类似EMT的变化,这与E-钙黏蛋白启动子甲基化谱的改变同时发生,并且作为最早的事件之一,可能促成引发结膜瘢痕形成的过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/763020c2585b/fcimb-07-00253-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/c79c17fe021f/fcimb-07-00253-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/bbdc6eb83b91/fcimb-07-00253-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/763020c2585b/fcimb-07-00253-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/c79c17fe021f/fcimb-07-00253-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/e3f55fb6dfe3/fcimb-07-00253-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/64f35be29937/fcimb-07-00253-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/c81a670029c2/fcimb-07-00253-g0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa9b/5469886/763020c2585b/fcimb-07-00253-g0008.jpg

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