Dataset Information

A unique esophageal extracellular matrix proteome alters normal fibroblast function in severe eosinophilic esophagitis.

ABSTRACT:

Background

Eosinophilic esophagitis (EoE) is a chronic T_H2 disorder complicated by tissue fibrosis and loss of esophageal luminal patency. The fibrostenotic esophagus does not respond well to therapy, but profibrotic therapeutic targets are largely unclear.

Objective

Our aim was to utilize proteomics and primary cells as a novel approach to determine relevant profibrotic factors.

Methods

We utilized primary esophageal EoE and normal fibroblasts, their derivative extracellular matrixes (ECMs), an approach of fibroblast culture on autologous versus nonautologous ECM, and proteomics to elucidate EoE ECM proteins that dysregulate cellular function.

Results

We cultured esophageal fibroblasts from normal esophagi and esophagi from patients with severe EoE on autologous versus nonautologous ECM. The EoE ECM proteome shifted normal esophageal fibroblast protein expression. Proteomic analysis demonstrated that thrombospondin-1 is detected only in the EoE ECM, is central in the EoE ECM protein-protein interactome, is found at significantly elevated levels in biopsy specimens from patients with active EoE, and induces fibroblast collagen I production.

Conclusion

Fibroblasts from patients with EoE secrete a unique ECM proteome that reflects their in vivo state and induces collagen I and α-smooth muscle actin protein expression from normal fibroblasts. Thrombospondin-1 is a previously unappreciated profibrotic molecule in EoE.

SUBMITTER: Hsieh LY

PROVIDER: S-EPMC8342625 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

A unique esophageal extracellular matrix proteome alters normal fibroblast function in severe eosinophilic esophagitis.

Hsieh Lance Y LY Chiang Austin W T AWT Duong Loan D LD Kuo Chih-Chung CC Dong Stephanie X SX Dohil Ranjan R Kurten Richard R Lewis Nathan E NE Aceves Seema S SS

The Journal of allergy and clinical immunology 20210206 2

<h4>Background</h4>Eosinophilic esophagitis (EoE) is a chronic T<sub>H</sub>2 disorder complicated by tissue fibrosis and loss of esophageal luminal patency. The fibrostenotic esophagus does not respond well to therapy, but profibrotic therapeutic targets are largely unclear.<h4>Objective</h4>Our aim was to utilize proteomics and primary cells as a novel approach to determine relevant profibrotic factors.<h4>Methods</h4>We utilized primary esophageal EoE and normal fibroblasts, their derivative ...[more]

PMID: 33556465

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Project description:Background & aimsAn association of eosinophilic esophagitis (EoE) with esophageal dysmotility has been described, however, the related mechanism remains unclear. We aimed to evaluate clinical and physiologic characteristics, including esophageal distensibility, associated with secondary peristalsis in patients with EoE.MethodsA total of 199 consecutive adult patients with EoE (age, 18-78 y; 32% female) who completed a 16-cm functional luminal imaging probe (FLIP) during endoscopy were evaluated in a cross-sectional study. FLIP panometry contractile response (CR) patterns were classified as normal CR or borderline CR if antegrade contractions were present, and abnormal CRs included impaired/disordered CR, absent CR, or spastic-reactive CR. The distensibility plateau of the esophageal body and esophagogastric junction distensibility was measured with FLIP.ResultsFLIP CR patterns included 68 (34%) normal CR, 65 (33%) borderline CR, 44 (22%) impaired/disordered CR, 16 (8%) absent CR, and 6 (3%) spastic-reactive CR. Compared with normal CRs, abnormal CRs more frequently had reduced esophageal distensibility (distensibility plateau <17 mm in 56% vs 32%), greater total EoE reference scores (median, 5; interquartile range [IQR], 3-6 vs median, 4; IQR, 3-5) with more severe ring scores, and a greater duration of symptoms (median, 10 y; IQR, 4-23 y vs median, 7 y; IQR, 3-15 y). Mucosal eosinophil density, however, was similar between abnormal CRs and normal CRs (median, 34 eosinophils/high-power field [hpf]; IQR, 14-60 eosinophils/hpf vs median, 25 eosinophils/hpf; IQR, 5-50 eosinophils/hpf).ConclusionsAlthough normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.

Dataset Information

A unique esophageal extracellular matrix proteome alters normal fibroblast function in severe eosinophilic esophagitis.

Background

Objective

Methods

Results

Conclusion

Publications

A unique esophageal extracellular matrix proteome alters normal fibroblast function in severe eosinophilic esophagitis.

Similar Datasets

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