胆汁酸可增加胃细胞中产生组胺的酶——组氨酸脱羧酶的表达。
Bile acid increases expression of the histamine-producing enzyme, histidine decarboxylase, in gastric cells.
机构信息
Hye Jin Ku, Hee Ju Park, Department of Pediatrics, College of Medicine, Pusan National University, Busan 601-721, South Korea.
出版信息
World J Gastroenterol. 2014 Jan 7;20(1):175-82. doi: 10.3748/wjg.v20.i1.175.
AIM
To investigate the effect of bile acid on the expression of histidine decarboxylase (HDC), which is a major enzyme involved in histamine production, and gene expression of gastric transcription factors upon cooperative activation.
METHODS
HDC expression was examined by immunohistochemistry, reverse transcriptase polymerase chain reaction, and promoter assay in human gastric precancerous tissues, normal stomach tissue, and gastric cancer cell lines. The relationship between gastric precancerous state and HDC expression induced by bile acid was determined. The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated. MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor (FXR), small heterodimer partner (SHP), and caudal-type homeodomain transcription factor (CDX)1 expression plasmids. The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay.
RESULTS
Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases. Here, we show that bile acid increased the expression of HDC, which is a rate-limiting enzyme of the histamine production pathway. FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression. In addition, the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression. We confirmed similar expression patterns for HDC, CDX1, and SHP in patient tissues.
CONCLUSION
HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR, SHP, and CDX1.
目的
研究胆汁酸对组氨酸脱羧酶（HDC）表达的影响，HDC 是参与组氨酸生成的主要酶，同时研究其对胃转录因子的基因表达的协同激活作用。
方法
采用免疫组织化学、逆转录聚合酶链反应和启动子分析方法，检测人胃癌前病变组织、正常胃组织和胃癌细胞系中 HDC 的表达。确定胆汁酸诱导的胃前病变状态与 HDC 表达之间的关系。评估胃细胞中 HDC 表达与各种特定转录因子之间的关系。用法尼酯 X 受体（FXR）、小异二聚体伴侣（SHP）和尾型同源盒转录因子（CDX）1 表达质粒转染 MKN45 和 AGS 人胃癌细胞系。通过荧光素酶报告基因启动子分析监测各种转录因子对 HDC 表达的影响。
结果
胃中组胺的产生和分泌在胃酸分泌和胃疾病的发病机制中起关键作用。在这里，我们表明胆汁酸增加了 HDC 的表达，HDC 是组氨酸产生途径的限速酶。发现 FXR 是胆汁酸诱导 HDC 表达的主要调节转录因子。此外，转录因子 CDX1 和 SHP 协同增强了胆汁酸诱导的 HDC 基因表达的升高。我们在患者组织中证实了 HDC、CDX1 和 SHP 的相似表达模式。
结论
胃中 HDC 的产生与胆汁酸暴露及其相关的 FXR、SHP 和 CDX1 转录调节网络有关。
Zotero 插件