Maturational Characterization of Human Esophageal Fibroblasts in EoE

EoE 中人食管成纤维细胞的成熟特征

• 批准号: 8594772
• 负责人: Amanda Brooke Muir
• 金额: $ 6.27万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594772
• 关键词: 3-Dimensional; Adult; Affect; Age; Allergic Disease; Allergic inflammation; Bile Acids; Biopsy; Bolus Infusion; Cell Culture Techniques; Cell Line; Cells; Characteristics; Childhood; Chronic; Chronic Disease; Cicatrix; Complication; Conditioned Culture Media; Data; Deglutition Disorders; Dermal; Diagnosis; Disease; Eosinophilic Esophagitis; Epithelial; Epithelial Cells; Epithelium; Esophageal; Esophageal Dysphagia; Esophageal Tissue; Esophagus; Fibroblasts; Fibrosis; Food; Human; In Vitro; Infiltration; Inflammation; Lead; Life; Mesenchymal; Modeling; Myofibroblast; Natural History; Patients; Population; Recurrence; Reporting; Stimulus; TNF gene; Tissues; age group; age related; cytokine; disease natural history; eosinophil; epithelial to mesenchymal transition; fetal; food antigen; migration; novel; prevent; public health relevance; release factor; response

DESCRIPTION (provided by applicant): Eosinophilic esophagitis (EoE) is an allergic disease characterized by esophageal infiltration of eosinophils, diagnosed from childhood through adulthood. Esophageal fibrosis is the most serious complication of EoE, leading to dysphagia and esophageal food impaction starting in the second decade of life. Elucidating the mechanisms which lead to fibrosis is critical to understanding the natural history of EoE. Our preliminary data suggests that cross-talk between primary EoE esophageal epithelial cells (EPCs) and primary fetal esophageal fibroblast cells (FEF3) enhances FEF3 expression of profibrotic cytokines. However, our model is limited by its use of fetal fibroblasts, which are functionally distinct from pediatric and adult fibroblasts. To date, characterization of esophageal fibroblasts spanning pediatric and adult EoE populations has never been described. Our overall hypothesis is that esophageal fibroblasts from EoE subjects are phenotypically distinct from fibroblasts from non-EoE subjects, and that fibro genic characteristics of EoE fibroblasts are enhanced during human maturation. Using primary esophageal fibroblasts, we will characterize fibroblast cytokine responses and contractility, comparing responses between age-matched EoE and non-EoE subjects (Aim 1a). Age-related differences in fibrotic responses in EoE subjects ages 1-9 years, 10-17 years, and adults will be examined (Aim 1b). We will determine fibroblast responses to epithelial-derived factors in the context of physiologically relevant epithelial stimuli including acid/bile and EoE triggers (food antigens) (Aim 2a). Finally, the effects of these stimuli upon fibrosis will be examined using novel organotypic cell culture models of "living" esophageal tissue, constructed from primary EPCs and esophageal fibroblast cell lines (Aim 2b).

描述（由申请人提供）：嗜酸性粒细胞性食管炎（EoE）是一种以食管嗜酸性粒细胞浸润为特征的过敏性疾病，诊断时间为儿童期至成年期。食管纤维化是EoE最严重的并发症，在生命的第二个十年开始导致吞咽困难和食管食物嵌塞。阐明导致纤维化的机制对于理解EoE的自然历史至关重要。我们的初步数据表明，原代EoE食管上皮细胞（EPCs）和原代胎儿食管成纤维细胞（FEF3）之间的相互作用增强了原纤维化细胞因子FEF3的表达。然而，我们的模型受到其使用胎儿成纤维细胞的限制，胎儿成纤维细胞在功能上不同于儿童和成人成纤维细胞。到目前为止，食管的特征