期刊
GUT AND LIVER
卷 -, 期 -, 页码 -出版社
EDITORIAL OFFICE GUT & LIVER
DOI: 10.5009/gnl220394
关键词
Intestinal metaplasia; GATA4 transcription factor; Transcriptional activation; NF-?B signaling
GATA4 is upregulated and can form a positive feedback loop with CDX2 to trans-activate MUC2 in GIM. NF-Kappa B signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.
Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gas-tric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunopre-cipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids.Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-Kappa B ac-tivation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa.Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to trans-activate MUC2 in GIM. NF-Kappa B signaling is involved in the upregulation of GATA4 by chenodeoxy-cholic acid. (Gut Liver, Published online March 2, 2023)
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