Role of Kruppel-Like Factor 5 in Deoxycholic Acid-Mediated Intestinal Transdifferentiation of Esophageal Squamous Epithelium

Barrett's esophagus (BE) is an acquired condition in which normal squamous epithelium is replaced with metaplastic columnar epithelium as a consequence of gastroesophageal reflux disease. BE is known as a precursor of esophageal adenocarcinoma. Currently, the molecular mechanism underlying epit...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Cancer 2019-01, Vol.10 (22), p.5597-5607
Main Authors: Xia, Yiju, Fang, Yu, Zhang, Haoxiang, Shen, Caifei, Wang, Pu, Yan, Wu, Li, Jingwen, Xu, Yin, Shao, Shunzi, Zhang, Yafei, Yu, Xiaona, Peng, Zhihong, Peng, Guiyong, Chen, Wensheng, Fang, Dianchun
Format: Article
Language:English
Subjects:
Acids
Bile
Biopsy
Cancer
Endoscopy
Esophagus
Experiments
Gastroesophageal reflux
Kinases
Pathogenesis
Pathophysiology
Research Paper
Small intestine
Stem cells
Transcription factors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Barrett's esophagus (BE) is an acquired condition in which normal squamous epithelium is replaced with metaplastic columnar epithelium as a consequence of gastroesophageal reflux disease. BE is known as a precursor of esophageal adenocarcinoma. Currently, the molecular mechanism underlying epithelial metaplasia in BE patients remains unknown. Therefore, we investigated the role of Krüppel-like factor 5 (KLF5) signaling in the initiation of BE-associated metaplasia. Sprague-Dawley (SD) rats were used to create a surgical model of bile reflux injury. Immunohistochemistry was performed to analyze human and mouse esophageal specimens. Human esophageal squamous epithelial (HET-1A) cells were treated with bile acid and used in transfection experiments. Quantitative real-time PCR and western blot analysis were performed to detect the expression of KLF5, CDX2, MUC2 and villin. Epithelial tissue from both the rat BE model and human BE patients strongly expressed KLF5, CDX2, MUC2, and villin. Bile acid treatment also increased the expression of KLF5, CDX2, MUC2 and villin in esophageal epithelial cells in a time-dependent manner. Moreover, siRNA-mediated knockdown of KLF5 blocked the expression of CDX2, MUC2 and villin, but transfection of a KLF5 expression vector into esophageal epithelial cells promoted their transdifferentiation into columnar-like cells, as demonstrated by increased expression of the intestinal markers CDX2, MUC2 and villin. Thus, in addition to its function as a transcription factor, KLF5 may be linked to an increased risk of BE development.
ISSN:1837-9664
1837-9664
DOI:10.7150/jca.30050