| RRC ID |
31028
|
| 著者 |
Wang DH, Tiwari A, Kim ME, Clemons NJ, Regmi NL, Hodges WA, Berman DM, Montgomery EA, Watkins DN, Zhang X, Zhang Q, Jie C, Spechler SJ, Souza RF.
|
| タイトル |
Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett's metaplasia.
|
| ジャーナル |
J Clin Invest
|
| Abstract |
Metaplasia can result when injury reactivates latent developmental signaling pathways that determine cell phenotype. Barrett's esophagus is a squamous-to-columnar epithelial metaplasia caused by reflux esophagitis. Hedgehog (Hh) signaling is active in columnar-lined, embryonic esophagus and inactive in squamous-lined, adult esophagus. We showed previously that Hh signaling is reactivated in Barrett's metaplasia and overexpression of Sonic hedgehog (SHH) in mouse esophageal squamous epithelium leads to a columnar phenotype. Here, our objective was to identify Hh target genes involved in Barrett's pathogenesis. By microarray analysis, we found that the transcription factor Foxa2 is more highly expressed in murine embryonic esophagus compared with postnatal esophagus. Conditional activation of Shh in mouse esophageal epithelium induced FOXA2, while FOXA2 expression was reduced in Shh knockout embryos, establishing Foxa2 as an esophageal Hh target gene. Evaluation of patient samples revealed FOXA2 expression in Barrett's metaplasia, dysplasia, and adenocarcinoma but not in esophageal squamous epithelium or squamous cell carcinoma. In esophageal squamous cell lines, Hh signaling upregulated FOXA2, which induced expression of MUC2, an intestinal mucin found in Barrett's esophagus, and the MUC2-processing protein AGR2. Together, these data indicate that Hh signaling induces expression of genes that determine an intestinal phenotype in esophageal squamous epithelial cells and may contribute to the development of Barrett's metaplasia.
|
| 巻・号 |
124(9)
|
| ページ |
3767-80
|
| 公開日 |
2014-9-1
|
| DOI |
10.1172/JCI66603
|
| PII |
66603
|
| 解説 |
ヒトバレット食道表皮細胞を用いGli1トランスクリプションアクチベーターがGli結合領域を活性化するか調べるために8×3′Gli-BS-delta51-LucIIが使用されました。
また、ネガティブコントロールとして8xm3′Gli-BS-delta51-LucIIが使用されました。
|
| PMID |
25083987
|
| PMC |
PMC4151220
|
| MeSH |
Animals
Barrett Esophagus / etiology*
Barrett Esophagus / metabolism
Esophagus / embryology*
Female
Hedgehog Proteins / physiology*
Hepatocyte Nuclear Factor 3-beta / analysis
Hepatocyte Nuclear Factor 3-beta / genetics
Hepatocyte Nuclear Factor 3-beta / physiology*
Kruppel-Like Transcription Factors
Mice
Mice, Inbred C57BL
Mucin-2 / genetics
Mucoproteins / genetics
Oncogene Proteins
SOX9 Transcription Factor / physiology
Signal Transduction / physiology*
Zinc Finger Protein GLI1
|
| IF |
11.864
|
| 引用数 |
51
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| リソース情報 |
| 遺伝子材料 |
8x3'Gli-BS-delta51-LucII (RDB08061)
8xm3'Gli-BS-delta51-LucII (RDB08062). |
