Abstract：
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-β, 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 cytokines 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-1β and TNFα, but not TGFβ. 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 TNFα and IL-1β-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-β and granulocytes, which may have important implications in treatment of EoE.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Muir AB,Lim DM,Benitez AJ,Modayur Chandramouleeswaran P,Lee AJ,Ruchelli ED,Spergel JM,Wang MLdoi
10.1016/j.yexcr.2012.12.002subject
Has Abstractpub_date
2013-04-01 00:00:00pages
850-9issue
6eissn
0014-4827issn
1090-2422pii
S0014-4827(12)00479-Xjournal_volume
319pub_type
杂志文章abstract：:A sufficient supply molecular oxygen is essential for the maintenance of physiologic metabolism and bioenergetic homeostasis for most metazoans. For this reason, mechanisms have evolved for eukaryotic cells to adapt to conditions where oxygen demand exceeds supply (hypoxia). These mechanisms rely on the modification o...
journal_title：Experimental cell research
pub_type： 杂志文章,评审
doi：10.1016/j.yexcr.2017.02.024
更新日期：2017-07-15 00:00:00
abstract：:This study was designed to elucidate the mechanisms involved in elevated cell death arising from an altered endogenous oxidant state. Increased levels of cell death were detected in cells lacking Gpx1 following the addition of exogenous H2O2. This increased apoptosis correlated with a down-regulation in the activation...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2004.07.018
更新日期：2004-11-01 00:00:00
abstract：:The expression level of DNA polymerase beta was determined in various mouse tissues. Northern blot hybridization analysis using rat cDNA as a probe revealed that the mRNA of about 1.5 kb for this enzyme is present in all kinds of tissues examined, but its content widely varies among tissues; the most abundant DNA poly...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(89)90191-2
更新日期：1989-03-01 00:00:00
abstract：:We previously identified a novel centrosomal protein CPAP, which carries a 112-residue motif that is essential for microtubule destabilization. In this report, we define both the microtubule (MT) binding and destabilizing domains in human CPAP and analyze the mutations that affect its MT-destabilizing activity. Analys...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2008.05.012
更新日期：2008-08-15 00:00:00
abstract：:There is increasing evidence that basic fibroblast growth factor (bFGF) plays an important role in cell proliferation, differentiation, and survival in various systems. In the eye, although a truncated, dominant negative bFGF receptor in transgenic mice induced defective lens development and caused lens fiber cells to...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1999.4450
更新日期：1999-05-25 00:00:00
abstract：:The MUC1 mucin is a large membrane-tethered glycoprotein that shows differential expression in many adenocarcinomas, where it contributes to their invasive and metastatic properties. We previously identified DNase I hypersensitive sites at -750 and -250 bp in the human MUC1 gene promoter and showed concordance between...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2005.04.008
更新日期：2005-08-01 00:00:00
abstract：:In low serum (0.2%) medium, ascorbate stimulates primary avian tendon cells to increase procollagen synthesis from 12 to 50% of total protein synthesis. This is reversibly blocked by an increase of serum levels from 0.2 to 3%. Ascorbate in low serum medium has been shown previously to stimulate the procollagen pathway...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(88)90330-8
更新日期：1988-06-01 00:00:00
abstract：:Cleavage of specific protein subsets is a key event in the execution of apoptosis. Protein degradation may serve for the structural alterations that result in cell self-destruction, but it may also function as a switch in the decisions between apoptosis and necrosis or apoptosis and cell proliferation. Here, we show t...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1997.3850
更新日期：1998-02-01 00:00:00
abstract：:Growth factors and cytokines initiate multiple signal transduction pathways that lead to cell survival, cell cycle progression or differentiation. A common feature of these pathways is increased cellular metabolism and glucose uptake. Furthermore, the energy requirements of many cancers and transformed cell lines are ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2003.10.027
更新日期：2004-02-15 00:00:00
abstract：:The establishment of cell lines allows reproductible in vitro studies that would be far more difficult to perform using primary cells that rapidly undergo phenotypical alterations in culture. The purpose of this work was to establish an endothelial cell line appropriate for in vitro study of endothelial cell activatio...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1997.3831
更新日期：1998-01-10 00:00:00
abstract：:Pair formation in the hypotrichous ciliate Euplotes octocarinatus is a poorly understood phenomenon. In order to obtain information about the molecules involved in this process, we compared ciliary and cell body-associated glycoconjugates of non-mating-competent, mating-competent, and conjugating cells. Detection of g...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1995.1114
更新日期：1995-04-01 00:00:00
abstract：:The rate-limiting step in melanogenesis is catalyzed by tyrosinase, a multifunctional enzyme encoded by the albino locus. We have previously reported that depletion of protein kinase C by long-term treatment of B16 mouse melanoma cells with phorbol dibutyrate (PDBu) prevented cell density-dependent melanogenesis. This...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1997.3773
更新日期：1997-11-25 00:00:00
abstract：:Neuromedin B (NMB) is one of the bombesin-like peptides in mammals. Recently, bombesin-like peptides have been characterized as growth factors in highly vascularized tumors. In this study, we report that NMB potently stimulates in vivo neovascularization in a mouse Matrigel plug and the sprouting of endothelial cells ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2009.08.009
更新日期：2009-11-15 00:00:00
abstract：:Profilin is one of the major components controlling actin polymerization. Here, profilin I was located in fibroblasts and HeLa cells by the use of two different sets of affinity-purified antibodies. Both antibody preparations labeled nuclei in a speckle-like pattern and displayed extensive colocalization with small nu...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/s0014-4827(03)00102-2
更新日期：2003-05-15 00:00:00
abstract：:PDGF acts as an autocrine and paracrine factor in certain tumors through upregulation of the PDGF beta-receptor expression. In order to elucidate the control mechanism for the receptor expression, we have isolated an enhancer from two P1 clones that together contain a 102 kb NotI region covering the entire human PDGFR...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2006.03.005
更新日期：2006-07-01 00:00:00
abstract：:There is at present a controversy in the literature whether MSCs are susceptible to spontaneous in vitro transformation or not. Several groups have reported spontaneous transformation of MSCs from various species. However, some of these reports were not true transformations and later proven to be due to cross-contamin...
journal_title：Experimental cell research
pub_type： 评论,杂志文章
doi：10.1016/j.yexcr.2011.12.009
更新日期：2012-03-10 00:00:00
abstract：BACKGROUND:Müller cell gliosis not only plays an important physiological role by maintaining retinal neuronal homeostasis but is also associated with multiple pathological events in the retina, including optic nerve crush (ONC) injury. Modulating Müller cell gliosis contributes to the creation of a permissive environme...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2019.01.009
更新日期：2019-02-15 00:00:00
abstract：:Transforming growth factor-beta (TGF-beta) induces apoptosis in fetal rat hepatocytes. However, a subpopulation of these cells survives, concomitant with changes in phenotype, reminiscent of an epithelial-mesenchymal transition (EMT). We have previously suggested that EMT might confer cell resistance to apoptosis (Val...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2006.05.017
更新日期：2006-09-10 00:00:00
abstract：:High throughput RNA sequencing techniques have revealed that a large fraction of the genome is transcribed into long non-coding RNAs (lncRNAs). Unlike canonical protein-coding genes, lncRNAs do not contain long open reading frames (ORFs) and tend to be poorly conserved across species. However, many of them contain sma...
journal_title：Experimental cell research
pub_type： 杂志文章,评审
doi：10.1016/j.yexcr.2020.111940
更新日期：2020-06-01 00:00:00
abstract：:The voltage-gated potassium channel, Kv1.3, plays an important role in regulating membrane excitability in diverse cell types ranging from T-lymphocytes to neurons. In the present study, we test the hypothesis that the C-terminal PDZ binding domain modulates the function and localization of Kv1.3. We created a mutant ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2011.06.009
更新日期：2011-10-01 00:00:00
abstract：:LMX1B is a LIM-homeodomain transcription factor essential for development. Putative LMX1B target genes have been identified through mouse gene targeting studies, but their identity as direct LMX1B targets remains hypothetical. We describe here the first molecular characterization of LMX1B target gene regulation. Micro...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2008.10.012
更新日期：2009-01-01 00:00:00
abstract：:The calcium/calmodulin-dependent protein phosphatase calcineurin is required for the induction of transcriptional events that initiate and promote myogenic differentiation. An important effector for calcineurin in striated muscle is the transcription factor myocyte enhancer factor 2 (MEF2). The targeting of the enzyme...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2012.12.016
更新日期：2013-02-15 00:00:00
abstract：:The male fetal lung begins to synthesize surfactant later in gestation than the female. This delay appears to be caused by androgens. We hypothesized that male fetal lung differentiation is delayed as a consequence of an extended phase of growth which is elicited by androgens. We observed that in vivo fetal lung prote...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(90)90281-e
更新日期：1990-05-01 00:00:00
abstract：:Differentiation of endoderm into intestinal epithelium is initiated at E13.5 of mouse development when there are significant changes in morphology resulting in the conversion of undifferentiated stratified epithelium into a mature epithelial monolayer. Here we demonstrate that monolayer formation is associated with th...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2004.10.006
更新日期：2005-02-15 00:00:00
abstract：:Repeated injury to the stratum corneum of mammalian skin (caused by friction, soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening. Functionally, these changes serve to restore the cutaneous barrier and protect the organism. To better understand the molecular and cellular basis of this response,...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2007.04.021
更新日期：2007-08-15 00:00:00
abstract：:Despite an increasing interest in the role of the p53 tumour suppressor protein in embryonic stem cells, not much is known about its regulation in this cell type. We show that the relatively high amount of p53 protein correlates with a higher amount of p53 RNA in ES cells compared to differentiated cells. Moreover, p5...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2010.06.006
更新日期：2010-09-10 00:00:00
abstract：:1,25-dihydroxyvitamin D(3) (VD(3)) induces differentiation in a number of leukemia cell lines and under various conditions is able to either stimulate or inhibit nuclear factor kappa B (NF-kappaB) activity. Here we report a time-dependent biphasic regulation of NF-kappaB in VD(3)-treated HL-60 leukemia cells. After VD...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2007.02.022
更新日期：2007-05-01 00:00:00
abstract：:In confluent keratinocyte monolayers, desmosomal adhesion gradually becomes calcium-independent and this is associated with an increase in the strength of intercellular adhesion (hyper-adhesion). In this study, we investigated the functional and molecular significance of hyper-adhesion in a system challenged by autoim...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2009.10.005
更新日期：2010-02-15 00:00:00
abstract：:In culture, nontransformed human diploid fibroblasts divide a limited number of times, resulting in a nonproliferating senescent cell culture which exhibits an altered pattern of gene expression. Previously we reported that an early event in the process of replicative senescence was an increase in the synthesis of two...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1996.0326
更新日期：1996-11-01 00:00:00
abstract：:The effect of transferrin was tested on osteoblastic cells (clone MC3T3-E1) cultured in serum-free medium containing 1% bovine serum albumin (BSA). Transferrin (Tf) stimulated increases of protein content and protein synthesis, but not of DNA content and cell number, in the cells. This protein also increased alkaline ...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/0014-4827(84)90465-8
更新日期：1984-07-01 00:00:00
