Deoxycholic acid (DCA) confers an intestinal phenotype on esophageal squamous epithelium via induction of the stemness-associated reprogramming factors OCT4 and SOX2.
Barrett's esophagus (BE) is essentially a metaplasia in which the normal stratified squamous epithelium is replaced by columnar epithelium. This study focuses on the involvement of OCT4 and SOX2, 2 key cell-reprogramming factors, in the deoxycholic acid (DCA)-induced expression of the intestinal hallmarks Cdx2 and MUC2 using both in vivo and in vitro models. Up-regulated expression of OCT4 and down-regulated expression of SOX2 were observed in BE compared with normal esophagus and esophagitis. Consistent with the data in vivo, DCA induced time-dependent expression of OCT4 at both the mRNA and protein levels and decreased nuclear expression of SOX2 in Het-1A cells. Down-regulation of OCT4 expression by siRNA abrogated DCA-induced expression of Cdx2 and MUC2, whereas siRNA against SOX2 significantly upregulated the expression of both Cdx2 and MUC2. Our data indicate that both OCT4 and SOX2 play important roles in the development of BE triggered by bile acid reflux.
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Caifei
C
Shen
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Haoxiang
H
Zhang
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Pu
P
Wang
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Ji
J
Feng
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Jingwen
J
Li
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Yin
Y
Xu
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Anran
A
Zhang
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Shunzi
S
Shao
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Xiaona
X
Yu
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Wu
W
Yan
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Yiju
Y
Xia
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Jiali
J
Hu
a Department of Gastroenterology , Southwest Hospital, Third Military Medical University , Chongqing , China.
Dianchun
D
Fang
D000818:Animals; D001471:Barrett Esophagus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071616:CDX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004941:Esophagitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C524625:MUC2 protein, human; D055262:Mucin-2; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D034741:RNA, Small Interfering; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D003840:Deoxycholic Acid
Barrett's esophagus; OCT4; SOX2; deoxycholic acid (DCA); intestinal metaplasia