Abstract

Gastroesophageal reflux disease (GERD), or acid reflux, affects 6-9 million people in the United States. It is characterized by a reflux of gastric acid and bile salts from the stomach into the esophagus, causing injuries to the esophagus known as Barrett's esophagus (BE). BE is the main risk factor for the development of esophageal adenocarcinoma (EAC), a devastating cancer in the esophagus whose molecular roots remain poorly understood. In recent years, evidence points to the esophageal epithelium itself as responsible for causing and promoting inflammation upon injury by gastric reflux, namely via an increase in inflammatory cytokine secretion. This project was focused on a cytokine of interest, Activin A, which is known for its importance during embryogenesis and stem cell differentiation. It has recently been studied for its role in inflammation and tumor formation, but not in the case of esophageal diseases. Here, we demonstrate that Activin A signaling in esophageal epithelial cells is heavily upregulated shortly after exposure to bile salts and acid. We show evidence that this upregulation causes an increase in cell migration upon a reconstituted extracellular matrix. We also provide further evidence that bile and acid injury causes epithelial cells to secrete cytokines, which drive inflammation. We show that the upregulated Activin A secretion and signaling plays an important role in promoting this inflammatory state. Finally, we provide evidence that bile salts and acid exposure, as well as increased Activin A signaling, causes esophageal epithelial cells to upregulate stem cell and transdifferentiation markers, supporting the latest theories on the origin of Barrett' esophagus stem cells as well as paligenosis.

Thesis Completion

2019

Semester

Spring

Thesis Chair/Advisor

Andl, Claudia

Degree

Bachelor of Science (B.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Degree Program

Biomedical Sciences

Language

English

Access Status

Open Access

Length of Campus-only Access

1 year

Release Date

5-1-2020

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