# Probing the Mechanisms of Fibroblast-Extracellular Matrix Interactions to Assess Disease Severity in Allergic Eosinophilic Esophagitis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $236,250

## Abstract

Project Summary
Eosinophilic esophagitis (EoE) is a chronic, antigen driven allergic disease that causes clinical symptoms of
vomiting, trouble swallowing, and poor growth in children. Due to chronic eosinophilic inflammation, the untreated
or therapy unresponsive EoE esophagus becomes rigid, narrowed, and dysmotile, resulting in food impactions.
Tissue remodeling includes histologic subepithelial fibrosis, angiogenesis and smooth muscle hypertrophy and
is the underlying mechanism for EoE complications. The subepithelial extracellular matrix (ECM) plays an
integral role in changing esophageal fibroblast and smooth muscle function. Pro-fibrotic factors can become
trapped in the ECM and matrix rigidity can alter structural cell functions. However, we currently lack an
understanding of the main molecular drivers of fibrosis in the EoE ECM and if the interactions between the ECM
and fibroblasts can reflect disease severity or predict the risk of esophageal narrowing in EoE. Further, there are
no easy ways to gauge therapeutic response to anti-remodeling compounds—a hinderance for patient care and
drug development. These issues create significant knowledge gaps for optimal patient care. While inflammation
initiates tissue remodeling, it is neither the sole propagator of esophageal dysfunction nor the best predictive
marker of pathological fibrosis. In this application we propose to use primary human esophageal fibroblasts from
patients with varying severities of EoE and from normal esophagi to understand the interaction between the ECM
and fibroblasts in order to decipher the most relevant molecules driving changes in fibroblast function. To
accomplish this, we will use both targeted protein analysis and an unbiased proteomic approach. We then plan
to use our experimental approach to assess the ability of potential anti-remodeling compounds to block ECM
induced changes in fibroblast function, thereby creating a potential personalized medicine platform for anti-
fibrotic compounds. We will align our in vitro findings with in vivo protein expression studies and with the long-
term disease trajectory using our well phenotyped longitudinal EoE cohort. We hypothesize that these studies
will determine novel and relevant proteins that alter the course of EoE and function as new therapeutic targets
for disease complications.

## Key facts

- **NIH application ID:** 10048452
- **Project number:** 1R21AI154353-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Seema S Aceves
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2020-05-22 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048452

## Citation

> US National Institutes of Health, RePORTER application 10048452, Probing the Mechanisms of Fibroblast-Extracellular Matrix Interactions to Assess Disease Severity in Allergic Eosinophilic Esophagitis (1R21AI154353-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10048452. Licensed CC0.

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