You are here

THE ROLE OF ACTIVIN A SIGNALING IN GASTRIC REFLUX-RELATED DISEASES AND THE PROGRESSION TO ESOPHAGEAL ADENOCARCINOMA

Download pdf | Full Screen View

Date Issued:
2019
Abstract/Description:
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.
Title: THE ROLE OF ACTIVIN A SIGNALING IN GASTRIC REFLUX-RELATED DISEASES AND THE PROGRESSION TO ESOPHAGEAL ADENOCARCINOMA.
0 views
0 downloads
Name(s): Roudebush, Cedric J., Author
Andl, Claudia, Committee Chair
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2019
Publisher: University of Central Florida
Language(s): English
Abstract/Description: 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.
Identifier: CFH2000485 (IID), ucf:45887 (fedora)
Note(s): 2019-05-01
B.S.
College of Medicine, Burnett School of Biomedical Sciences
Bachelors
This record was generated from author submitted information.
Subject(s): Activin A
GERD
Inflammation
Barrett's Esophagus
BE Stem Cells
Transdifferentiation
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFH2000485
Restrictions on Access: campus 2020-05-01
Host Institution: UCF

In Collections