Role of Kruppel-Like Factor 5 in Deoxycholic Acid-Mediated Intestinal Transdifferentiation of Esophageal Squamous Epithelium
| Autor: | Ya-Fei Zhang, Zhihong Peng, Caifei Shen, Dian-Chun Fang, Yin Xu, Shunzi Shao, Haoxiang Zhang, Xiaona Yu, Jingwen Li, Yiju Xia, Guiyong Peng, Pu Wang, Wensheng Chen, Wu Yan, Yu Fang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
transdifferentiation digestive system Barrett's esophagus 03 medical and health sciences 0302 clinical medicine Metaplasia medicine Esophagus CDX2 biology Chemistry Transdifferentiation KLF5 medicine.disease digestive system diseases Epithelium 030104 developmental biology medicine.anatomical_structure Oncology deoxycholic acid 030220 oncology & carcinogenesis Epithelial Metaplasia biology.protein Cancer research medicine.symptom Villin Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| DOI: | 10.7150/jca.30050 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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