ArticleThe Journal of allergy and clinical immunology2026
Effects of proton pump inhibitors on remodeling and fibrosis in eosinophilic esophagitis.
Article in The Journal of allergy and clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEosinophilic esophagitis (EoE) is a progressive fibrostenotic disease. Although proton pump inhibitors (PPIs) are a first-line EoE treatment due to their anti-inflammatory effects, their effects on remodeling/fibrosis-likely driven in part by TGF-β-remain uncertain.
objectivesTo elucidate remodeling/fibrosis effects, this study evaluated whether PPIs impact the esophageal transcriptome of PPI-responsive EoE and counteract TGF-β‒induced fibrotic responses in human primary esophageal fibroblasts (HEFs).
methodsProspectively collected paired esophageal biopsies from patients with EoE pre‒/post‒PPI treatment were analyzed by RNA sequencing (RNA-seq). Histologic responsiveness to PPIs was defined as responders (<15 eosinophils/high-power field, n = 10) or nonresponders (≥15 eosinophils/high-power field, n = 9). The ability of PPIs (esomeprazole, omeprazole) to attenuate in vitro, TGF-β‒mediated remodeling/fibrosis in HEFs was analyzed by quantitative PCR, RNA-seq, Western blotting, immunofluorescence, cell migration assays, and reactive oxygen species measurements.
resultsIn PPI responders, we identified 746 differentially expressed genes pre‒/post‒PPI treatment (≥2-fold change, P < .05), particularly those enriched in remodeling/fibrosis. In HEFs, TGF-β increased collagen I and α-smooth muscle actin expression via SMAD2/3 phosphorylation; however, PPIs attenuated these responses. RNA-seq revealed that PPIs reversed approximately 30% of TGF-β‒induced changes overlapping with fibrotic responses; 78 genes were concordantly modulated between patient biopsies and HEFs. Functional assays further confirmed that PPIs reduced TGF-β-induced collagen deposition, fibroblast motility, and reactive oxygen species production.
conclusionsPPIs modulate remodeling-/fibrosis-related gene expression in patients with EoE and inhibit TGF-β‒induced profibrotic responses in HEFs, supporting antifibrotic potential that may help limit fibrostenotic progression in EoE.
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