A Unique Esophageal Extracellular Matrix Proteome Alters Normal Fibroblast Function in Severe Eosinophilic Esophagitis.

Austin Chiang

Immunology Center of Georgia

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Article

Peer-review

Abstract

Eosinophilic esophagitis (EoE) is a chronic Th2 disorder complicated by tissue fibrosis and loss of esophageal luminal patency. The fibrostenotic esophagus does not respond well to therapy but pro-fibrotic therapeutic targets are largely unclear. To utilize proteomics and primary cell as a novel approach to determine relevant pro-fibrotic factors. We utilized primary esophageal EoE and normal fibroblasts, their derivative extracellular matrixes (ECMs), an approach of fibroblast culture on autologous versus opposing ECM, and proteomics to elucidate EoE ECM proteins that dysregulate cellular function. We cultured esophageal fibroblasts from normal or severe EoE esophagi on autologous versus opposing extracellular matrix (ECM). The EoE ECM proteome shifted normal esophageal fibroblast protein expression. Proteomic analysis demonstrated that thrombospondin-1 (TSP-1) is detected only in the EoE ECM, is central in the EoE ECM protein-protein interactome, is significantly elevated in active EoE biopsies, and induces fibroblast collagen I production. EoE fibroblasts 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. TSP-1 is a previously unappreciated pro-fibrotic molecule in EoE. The novel approach of culturing tissue fibroblasts on autologous versus opposing ECM has clinical utility for identifying previously unappreciated disease-specific druggable ECM targets in EoE and, potentially other, fibrotic disorders.

Publication Information

Output type

Scholary Output:

Contribution to journal

Article

Peer-review

Original language

Undefined

Journal (Volume, Issue Number)

The Journal of Allergy and Clinical Immunology

Publication milestones

Published - 02/05/2021

Publication status

Published - 02/05/2021

ISSN

0091-6749

Publication IDs

ORCID: /0000-0001-6514-5612/work/88441601
PubMed: 33556465
Scopus: 85106222999

Access to documents

10.1016/j.jaci.2021.01.023

Link

https://doi.org/10.1016/j.jaci.2021.01.023, opens in new tab

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