Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma.
Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma.
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作者：
Hong J;Behar J;Wands J;Resnick M;Wang LJ;DeLellis RA;Lambeth D;Souza RF;Spechler SJ;Cao W
从Barrett食管（BO）进展为食管腺癌（OA）的机制尚未完全了解。胆汁酸可能在这一进程中发挥重要作用。本研究旨在探讨NADPH氧化酶NOX 5-S和新型胆汁酸受体TGR 5在牛磺脱氧胆酸（TDCA）诱导的细胞增殖增加中的作用。使用Lipofectamine 2000或Amaxa-Nucleofector-System转染人巴雷特细胞系BAR-T和OA细胞系FLO。通过实时PCR测量mRNA。通过荧光测定法测量H2 O2。通过测量胸苷掺入来确定细胞增殖。FLO细胞中存在NOX 5-S。TDCA显著增加FLO和BAR-T细胞中NOX 5-S表达、H2 O2产生和胸苷掺入。这种胸苷掺入的增加通过敲低NOX 5-S而显著降低。TGR 5 mRNA和蛋白水平在OA组织中显著高于正常食管粘膜或Barrett粘膜。TGR 5的敲低显著抑制了TDCA诱导的FLO和BAR-T细胞中NOX 5-S表达、H2 O2产生和胸苷掺入的增加。TGR 5的过表达显著增强了TDCA对FLO细胞的作用。TGR 5受体与Gαq和Gαi-3蛋白偶联，但只有Gαq介导TDCA诱导的NOX 5-S表达、H2 O2产生和胸苷掺入增加。TDCA诱导的细胞增殖增加依赖于BAR-T和FLO细胞中NOX 5-S表达的上调。TDCA诱导的NOX 5-S表达可能通过TGR 5受体和Gαq蛋白的激活介导。我们的数据可以提供潜在的目标，以预防和/或治疗巴雷特的OA。
Mechanisms of the progression from Barrett’s oesophagus (BO) to oesophageal adenocarcinoma (OA) are not fully understood. Bile acids may play an important role in this progression. The aim of this study is to examine the role of NADPH oxidase NOX5-S and a novel bile acid receptor TGR5 in taurodeoxycholic acid (TDCA)-induced increase in cell proliferation. Human Barrett’s cell line BAR-T and OA cell line FLO were transfected by using Lipofectamine 2000 or Amaxa-Nucleofector-System. mRNAs were measured by real-time PCR. H2O2 was measured by a fluorescent assay. Cell proliferation was determined by measurement of thymidine incorporation. NOX5-S was present in FLO cells. TDCA significantly increased NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. This increase in thymidine incorporation was significantly reduced by knockdown of NOX5-S. TGR5 mRNA and protein levels were significantly higher in OA tissues than in normal oesophageal mucosa or Barrett’s mucosa. Knockdown of TGR5 markedly inhibited TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO and BAR-T cells. Overexpression of TGR5 significantly enhanced the effects of TDCA in FLO cells. TGR5 receptors were coupled with Gαq and Gαi-3 proteins, but only Gαq mediated TDCA-induced increase in NOX5-S expression, H2O2 production and thymidine incorporation in FLO cells. TDCA-induced increase in cell proliferation depends on upregulation of NOX5-S expression in BAR-T and FLO cells. TDCA-induced NOX5-S expression may be mediated by activation of the TGR5 receptor and Gαq protein. Our data may provide potential targets to prevent and/or treat Barrett’s OA.
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影响因子：
5
作者：
Bajpai, Manisha;Liu, Jianying;Das, Kiron M.
通讯作者：
Das, Kiron M.
DOI：
10.1016/s1091-255x(98)80021-8
发表时间：
1998-05-01
期刊：
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
影响因子：
--
作者：
Fein, M;Peters, J H;DeMeester, T R
通讯作者：
DeMeester, T R
影响因子：
9.8
作者：
El-Serag, HB;Aguirre, TV;Sampliner, RE
通讯作者：
Sampliner, RE
DOI：
10.1016/j.bbrc.2005.01.139
发表时间：
2005-04-01
影响因子：
3.1
作者：
Katsuma, S;Hirasawa, A;Tsujimoto, G
通讯作者：
Tsujimoto, G
影响因子：
4.7
作者：
Jenkins, Gareth J. S.;D'Souza, Francis R.;Baxter, John N.
通讯作者：
Baxter, John N.