A unique esophageal extracellular matrix proteome alters normal fibroblast function in severe eosinophilic esophagitis.
J Allergy Clin Immunol
; 148(2): 486-494, 2021 08.
Article
in En
| MEDLINE
| ID: mdl-33556465
ABSTRACT
BACKGROUND:
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 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proteome
/
Esophagus
/
Extracellular Matrix
/
Eosinophilic Esophagitis
/
Fibroblasts
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2021
Document type:
Article