Studying the transcriptomic effects of the IL-20 cytokine subfamily on the esophageal epithelium
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PROVIDER: PRJNA751235 | ENA |
REPOSITORIES: ENA
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Project description:Esophagus organoids were subjected to a cytokine treatment, and the sample were studied with RNA-sequencing.
2022-05-20 | GSE181261 | GEO
Project description:Introduction Disruption of the epithelial barrier can induce eosinophilic esophagitis (EoE), a TH2-mediated food- and aeroallergen associated chronic inflammatory disease 1, 2. The expression of IL-20 subfamily cytokines, IL-19, IL-20 and IL-24, is increased in TH2-mediated diseases, yet their function in EoE is unknown. Methods Combining RNA-sequencing (RNA-seq) and proteome analysis, we have examined the effects of the IL-20 subfamily on esophageal epithelial cells using patient-derived organoids and an experimental EoE mouse model. Results When stimulated with IL-20 subfamily cytokines patient-derived esophageal organoids showed decreased expression of Filaggrin (FLG) and Filaggrin 2 (FLG2) responsible for epithelial cornification. In agreement, EoE patients with active inflammation showed elevated IL-20 subfamily cytokines and decreased FLG and FLG2 expression. Topical corticosteroid treatment in EoE patients restored filaggrin expression, while reducing IL-20 subfamily cytokines. Abolishment of IL-20 subfamily signalling in Il20R2-/- animals attenuated experimental EoE in an OVA-induced mouse model. In the esophageal keratinocyte cell line, KYSE-180, we identified IL-20 subfamily-induced STAT3 and MAPK (ERK1/2) pathway activation. However, Stat3fl/flKrt5cre mice with an epithelium specific deletion of Stat3 developed exacerbated experimental EoE with a pronounced decrease of Flg2. In line, combined stimulation of patient-derived esophageal organoids with IL-20 subfamily cytokines and pharmacological inhibition of STAT3 resulted in aggravated decrease of FLG and FLG2. In addition, pharmacological STAT3 inhibition resulted in reduced transepithelial electrical resistance (TEER) and increased macromolecular flux in patient-derived air liquid interface (ALI) cultures. Whereas, inhibition of the MAPK (ERK1/2) pathway hampered IL-20 subfamily induced TEER reduction and paracellular flux increment. Finally, MAPK (ERK1/2) inhibitor treatment reduced infiltrating CD45+ immune cells in the esophagus and alleviated experimental EoE in mice. Conclusion We discovered a novel regulatory function of the IL-20 subfamily for epithelial barrier integrity. Aberrant IL-20 subfamily signaling disturbs the epithelial barrier function, while abrogation of IL-20 subfamily and ERK1/2 signaling restores epithelial integrity and attenuates experimental EoE. Therefore, we propose that targeting the IL-20 subfamily pathway could present a novel therapeutic strategy for EoE treatment.
2023-05-10 | PXD031509 | Pride
Project description:We used RNA sequencing to identify differentially expressed genes during esophageal epithelial differentiation and in the presence of interleukin 13 using an air-liquid interface culture system. RNA sequencing was performed on a human esophageal epithelial cell line (EPC2-hTERT) grown submerged (day 8) or at the air-liquid interface (ALI) (day 14, untreated or treated with interleukin 13 [100 ng/mL])
2015-02-01 | E-GEOD-65335 | biostudies-arrayexpress
Project description:We identified spatially restricted transcription factors and found SOX15 expression confined to stratified esophageal epithelium, with attenuation in Barrett's esophagus. SOX15 binds esophagus-specific loci and its loss in human esophageal cells affected esophagus-specific transcripts
2015-11-09 | GSE62909 | GEO
Project description:The interplay between genetic and environmental factors during pregnancy can predispose to inflammatory diseases postnatally, including eosinophilic esophagitis (EoE), a chronic allergic disease triggered by food. Herein, we examined the effects of amniotic fluid (AF) on esophageal epithelial differentiation and responsiveness to proallergic stimuli. Multiplex analysis of AF revealed the expression of 66 cytokines, whereas five cytokines including IL-4 and thymic stromal lymphopoietin (TSLP) were not detected. Several proinflammatory cytokines including TNFα and IL-12 were highly expressed in the AF from women who underwent preterm birth, whereas EGF was the highest in term birth samples. Exposure of esophageal epithelial cells to AF resulted in transient phosphorylation of ERK1/2 and the transcription of early response genes, highlighting the direct impact of AF on esophageal epithelial cells. In a three-dimensional spheroid model, AF modified the esophageal epithelial differentiation program and enhanced the transcription of IL-13-target genes, including CCL26 and CAPN14, which encodes for a major genetic susceptibility locus for eosinophilic esophagitis. Notably, CAPN14 exhibited upregulation in spheroids exposed to preterm but not term AF following differentiation. Collectively, our findings call attention to the role of AF as a potential mediator of the intrauterine environment that influences subsequent esophageal disorders.
2024-08-01 | GSE256022 | GEO
Project description:Samples were obtained from 8 patients with Barrett's associated adenocarcinomas after transhiatal esophagectomy. Samples representative of the normal esophageal epithelium (N), Barrett’s esophagus (B) and esophageal adenocarcinomas (ADC) were obtained from every patient by experienced GI pathologists. RNA were extracted and samples were profiled for detection of genes differentially expressed in B and ADC relative to N and in ADC relative to B. Keywords: other
2004-11-18 | GSE1420 | GEO
Project description:We used RNA sequencing to identify differentially expressed genes during esophageal epithelial differentiation and in the presence of interleukin 13 using an air-liquid interface culture system.
2015-02-01 | GSE65335 | GEO
Project description:Many esophageal diseases arise in the context of chronic inflammation, but the role that esophageal epithelial cells play in initiating inflammation remains poorly understood. Since the IKKβ/NF-κB and STAT3 pathways are critical signaling hubs that drive inflammatory-mediated responses, we aimed to identify how these two pathways regulate gene expression in esophageal epithelial cells. In this study, we performed RNA-Seq analysis on esophageal epithelium from mice with overexpression of constitutively active Ikkb and/or loss of Stat3 specifically in esophageal epithelial cells.
2021-04-01 | GSE154129 | GEO
Project description:To investigate gene expression signature of the human esophageal epithelium we performed FACS sorting of the basal and the suprabasal layers from the esophageal biopsies based on the expression of podoplanin and E-cadherin.
2022-06-15 | GSE201154 | GEO
Project description:The esophagus is protected from the hostile environment by a stratified epithelium, which renews rapidly. Homeostasis of this epithelium is ensured by a rare population of stem cells in the basal layer: Keratin 15+ (Krt15+) cells. However, little is known about the molecular mechanisms regulating their distinct features, namely self-renewal, potency, and epithelial regeneration. Achaete-Scute Family BHLH Transcription Factor 2 (ASCL2) is strongly upregulated in Krt15+ stem cells and is known to contribute to stem cell maintenance in other tissues. Herein, we investigated the role of ASCL2 in maintaining homeostasis under normal and stress conditions in the esophageal epithelium. ASCL2 overexpression severely dysregulated cell differentiation and cell fate. Proliferation was also reduced due potentially to a blockage in the G1 phase of the cell cycle or an induction of quiescence. Mass spectrometry analysis confirmed alterations in several proteins associated with differentiation and cell cycle. In addition, overexpression of ASCL2 enhanced resistance to radiation and chemotherapeutic drugs. Overall, these results denoted the role of ASCL2 as a key regulator of the proliferation-differentiation equilibrium in the esophageal epithelium.
2024-05-24 | PXD039477 | Pride