GATA4 Forms a Positive Feedback Loop with CDX2 to Transactivate MUC2 in Bile Acids-Induced Gastric Intestinal Metaplasia

作者全名："Yang, Xiaofang; Ye, Ting; Rong, Li; Peng, Hong; Tong, Jin; Xiao, Xiao; Wan, Xiaoqiang; Guo, Jinjun"

作者地址："[Yang, Xiaofang; Ye, Ting; Tong, Jin; Xiao, Xiao; Wan, Xiaoqiang; Guo, Jinjun] Chongqing Univ, Chongqing Univ Cent Hosp, Chongqing Emergency Med Ctr, Dept Gastroenterol,Sch Med, Chongqing, Peoples R China; [Rong, Li; Peng, Hong; Guo, Jinjun] Chongqing Med Univ, Bishan Hosp Chongqing, Dept Gastroenterol, Bishan Hosp, Chongqing, Peoples R China"

通信作者："Guo, JJ (通讯作者)，Chongqing Univ, Chongqing Univ Cent Hosp, Chongqing Emergency Med Ctr, Dept Gastroenterol,Sch Med, Chongqing, Peoples R China.; Guo, JJ (通讯作者)，Chongqing Med Univ, Bishan Hosp Chongqing, Dept Gastroenterol, Bishan Hosp, Chongqing, Peoples R China."

来源：GUT AND LIVER

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000944119800001

JCR分区：Q2

影响因子：3.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Intestinal metaplasia; GATA4 transcription factor; Transcriptional activation; NF-?B signaling

摘要："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)"

基金机构："Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technol-ogy Bureau) [2020FYYX084]; Chongqing Natural Science Foundation [cstc2019jscx-msxmX0202, CSTB2022NSCQ-MSX1257, cstc2018jcyjAX0006]; Department of Gastroenterology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing University School of Medicine"

基金资助正文："This work was supported by grants from the Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau, 2020FYYX084 to J.T.) , Chongqing Natural Science Foundation (cstc2019jscx-msxmX0202 to X.W., CSTB2022NSCQ-MSX1257 to L.R, cstc2018jcyjAX0006 to J.G.) . This work was supported by two professional pathologists, Li Peng and Jing Chen (Department of Gastroenterology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing University School of Medicine) ."