Esophageal epithelial and mesenchymal cross-talk leads to features of epithelial to mesenchymal transition in vitro
Esophageal epithelial and mesenchymal cross-talk leads to features of epithelial to mesenchymal transition in vitro
复制标题
DOI：
10.1016/j.yexcr.2012.12.002
复制
发表时间：
2013-04-01
影响因子：
3.7
通讯作者：
Wang, Mei-Lun
中科院分区：
文献类型：
--
作者：
Muir, Amanda B.;Lim, Diana M.;Wang, Mei-Lun
背景资料：食管纤维化是嗜酸性粒细胞性食管炎（EoE）的并发症，其归因于上皮下纤维化和上皮向间质转化（EMT），上皮细胞通过EMT获得间质特征。EoE-纤维化的两种原因的共同点是粒细胞衍生的TGF-β诱导靶细胞的肌成纤维细胞分化。迄今为止，食管上皮细胞作为效应细胞在食管纤维化中的作用尚未被探索。在此，我们调查了食管上皮细胞和成纤维细胞之间的串扰的后果，并确定profibrotic cytoldnes影响EMT的发展在vitro.Methods和结果：刺激的初级胎儿食管成纤维细胞（FEF 3）与条件培养基（CEM）从食管上皮细胞（EPC 2-hTERT），引发FEF 3细胞分泌IL-1 β和TNF α，但不TGF β。为了确定这些细胞因子是否以旁分泌方式向食管上皮细胞发出信号，用CEM刺激FEF 3细胞，然后将该成纤维细胞条件培养基（FCM）转移至EPC 2-hTERT细胞。上皮细胞FCM刺激增加了间充质标志物的表达，减少了E-cadherin的表达，EMT的特征是TNF α和IL-1 β依赖性。使用器官型培养模型，原代EoE上皮细胞表现出EMT的功能相比，非EoE细胞，对应的模式EMT在本地biopsizes.Conclusions：食管上皮细胞和成纤维细胞的串扰有助于食管纤维化。我们的研究结果表明，EMT的功能可以独立于TGF-β和粒细胞，这可能对EoE的治疗有重要意义。(C)2012 Elsevier Inc. All rights reserved.
Background: Esophageal fibrosis is a complication of eosinophilic esophagitis (EoE) which has been attributed to both subepithelial fibrosis and to epithelial to mesenchymal transition (EMT), a process by which epithelial cells acquire mesenchymal features. Common to both causes of EoE-fibrosis is the notion that granulocyte-derived TGF-beta, induces myofibroblast differentiation of the target cell. To date, the role of esophageal epithelial cells as effector cells in esophageal fibrosis has never been explored. Herein, we investigated consequences of cross-talk between esophageal epithelial cells and fibroblasts, and identified profibrotic cytoldnes which influence the development of EMT in vitro.Methods and results: Stimulation of primary fetal esophageal fibroblasts (FEF3) with conditioned media (CEM) from esophageal epithelial cells (EPC2-hTERT), primed FEF3 cells to secrete IL-1 beta and TNF alpha, but not TGF beta. To determine whether these cytokines signaled in a paracrine fashion to esophageal epithelial cells, FEF3 cells were stimulated with CEM, followed by transfer of this fibroblast conditioned media (FCM) to EPC2-hTERT cells. Epithelial FCM stimulation increased expression of mesenchymal markers and reduced E-cadherin expression, features of EMT which were TNF alpha and IL-1 beta-dependent. Using organotypic culture models, primary EoE epithelial cells exhibited features of EMT compared to non-EoE cells, corresponding to patterns of EMT in native biopsies.Conclusions: Esophageal epithelial cell and fibroblast cross-talk contributes to esophageal fibrosis. Our results suggest that features of EMT can develop independent of TGF-beta and granulocytes, which may have important implications in treatment of EoE. (C) 2012 Elsevier Inc. All rights reserved.