Presentation Title

Identification and Treatment of Activated Esophageal Lamina Propria Fibroblasts in a mouse model of Eosinophilic Esophagitis

Faculty Mentor

Glenn Furuta, Joanne Masterson

Start Date

18-11-2017 2:15 PM

End Date

18-11-2017 3:15 PM

Location

BSC-Ursa Minor 105

Session

Poster 3

Type of Presentation

Poster

Subject Area

health_nutrition_clinical_science

Abstract

Introduction-Eosinophilic esophagitis (EoE) is a rare gastrointestinal disease thought to be caused by food allergic reactions. EoE symptoms are related to esophageal dysfunction and include vomiting and feeding difficulties in children, and dysphagia and food impaction in adults (Furuta & Katzka, 2015). Chronic esophageal inflammation can increase the risk of developing fibrosis, esophageal strictures, and long-segment esophageal narrowing (Schoepfer et al., 2013). Although the histopathological implications of esophageal eosinophils have been carefully documented, mechanisms underlying esophageal strictures are not well understood. Alpha-smooth muscle actin (α-SMA) marks activated fibroblasts that reside in esophageal lamina propria (LP) that proliferate and secrete matrix proteins that are deposited in tissues and potentially causing them to be less distensible.

Hypothesis-Chronic eosinophilic inflammation will lead to increased α-SMA presence in the LP.

Methods- To induce EoE, mice that overexpress interleukin-5 in the esophagus were sensitized and challenged (intra-esophageal) with the irritant oxazolone to induce acute (3-challenges) or chronic (9-challenges) EoE, and treated with the glucocorticoid dexamethasone (Dex) which prevents tissue inflammation. Using immunohistochemical techniques, fibrosis was quantified in the LP counting α-SMA positive cells. Intensity measurement analysis of the LP was performed in the following four distinguished groups: acute inflammatory EoE untreated (EoEacute), chronic EoE untreated (EoEchronic), acute inflammatory EoE Dex-treated (EoEacute-DEX), and chronic EoE Dex-treated (EoEchronic-DEX).

Results- Compared to controls, EoEacute mice had no increase in LP-α-SMA positivity; however, compared to both of these groups EoEchronic mice had a significant increase in LP-α-SMA (1.5-fold; P<0.05). When treated with glucocorticoids LP-α-SMA expression normalized (EoEchronic-DEX; P=0.7).

Conclusion- Our novel findings indicated that activated fibroblasts increased in a mouse model of EoE and an accepted treatment for EoE in humans, can reverse this process.

Speculation- Activated fibroblasts are a novel therapeutic target for patients with EoE related strictures.

Summary of research results to be presented

Intensity measurement analysis of the LP was performed in the following four distinguished groups: acute inflammatory EoE untreated (EoEacute), chronic EoE untreated (EoEchronic), acute inflammatory EoE Dex-treated (EoEacute-DEX), and chronic EoE Dex-treated (EoEchronic-DEX). Compared to controls, EoEacute mice had no increase in LP-α-SMA positivity; however, compared to both of these groups EoEchronic mice had a significant increase in LP-α-SMA (1.5-fold; Pchronic-DEX; P=0.7). The results have provided evidence for increased activated fibroblast presence in a mouse model of chronic EoE, that are decreased by glucocorticoid treatment.

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Nov 18th, 2:15 PM Nov 18th, 3:15 PM

Identification and Treatment of Activated Esophageal Lamina Propria Fibroblasts in a mouse model of Eosinophilic Esophagitis

BSC-Ursa Minor 105

Introduction-Eosinophilic esophagitis (EoE) is a rare gastrointestinal disease thought to be caused by food allergic reactions. EoE symptoms are related to esophageal dysfunction and include vomiting and feeding difficulties in children, and dysphagia and food impaction in adults (Furuta & Katzka, 2015). Chronic esophageal inflammation can increase the risk of developing fibrosis, esophageal strictures, and long-segment esophageal narrowing (Schoepfer et al., 2013). Although the histopathological implications of esophageal eosinophils have been carefully documented, mechanisms underlying esophageal strictures are not well understood. Alpha-smooth muscle actin (α-SMA) marks activated fibroblasts that reside in esophageal lamina propria (LP) that proliferate and secrete matrix proteins that are deposited in tissues and potentially causing them to be less distensible.

Hypothesis-Chronic eosinophilic inflammation will lead to increased α-SMA presence in the LP.

Methods- To induce EoE, mice that overexpress interleukin-5 in the esophagus were sensitized and challenged (intra-esophageal) with the irritant oxazolone to induce acute (3-challenges) or chronic (9-challenges) EoE, and treated with the glucocorticoid dexamethasone (Dex) which prevents tissue inflammation. Using immunohistochemical techniques, fibrosis was quantified in the LP counting α-SMA positive cells. Intensity measurement analysis of the LP was performed in the following four distinguished groups: acute inflammatory EoE untreated (EoEacute), chronic EoE untreated (EoEchronic), acute inflammatory EoE Dex-treated (EoEacute-DEX), and chronic EoE Dex-treated (EoEchronic-DEX).

Results- Compared to controls, EoEacute mice had no increase in LP-α-SMA positivity; however, compared to both of these groups EoEchronic mice had a significant increase in LP-α-SMA (1.5-fold; P<0.05). When treated with glucocorticoids LP-α-SMA expression normalized (EoEchronic-DEX; P=0.7).

Conclusion- Our novel findings indicated that activated fibroblasts increased in a mouse model of EoE and an accepted treatment for EoE in humans, can reverse this process.

Speculation- Activated fibroblasts are a novel therapeutic target for patients with EoE related strictures.