Helicobacter pylori infection downregulates duodenal CFTR and SLC26A6 expressions through TGFβ signaling pathway.
Helicobacter pylori infection downregulates duodenal CFTR and SLC26A6 expressions through TGFβ signaling pathway.
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幽门螺杆菌感染通过TGFβ信号通路下调十二指肠CFTR和SLC26A6表达
DOI：
10.1186/s12866-018-1230-8
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发表时间：
2018-08-17
期刊：
影响因子：
4.2
通讯作者：
Tuo B
中科院分区：
文献类型：
--
作者：
Wen G;Deng S;Song W;Jin H;Xu J;Liu X;Xie R;Song P;Tuo B
幽门螺杆菌（H. pylori）感染诱发十二指肠溃疡的发病机制仍有待阐明。十二指肠黏膜碳酸氢盐分泌是抵御酸诱导的黏膜损伤的最重要保护因素。我们先前发现幽门螺杆菌感染下调十二指肠黏膜囊性纤维化跨膜传导调节因子（CFTR）和溶质相关载体26基因家族A6（SLC26A6）的表达及功能活性，这两者是介导十二指肠碳酸氢盐分泌的两种关键的十二指肠黏膜上皮细胞碳酸氢盐转运体。在本研究中，我们探讨了幽门螺杆菌感染诱导十二指肠CFTR和SLC26A6表达下调的机制。
我们发现幽门螺杆菌感染可使C57BL/6小鼠血清转化生长因子β（TGFβ）水平升高以及十二指肠黏膜TGFβ表达增加，同时使十二指肠黏膜CFTR和SLC26A6表达降低。人十二指肠上皮细胞（SCBN）实验结果显示，幽门螺杆菌可使SCBN细胞中TGFβ产生增加，CFTR和SLC26A6表达降低。TGFβ抑制剂SB431542可逆转幽门螺杆菌诱导的CFTR和SLC26A6表达降低。进一步的结果表明，TGFβ可直接降低SCBN细胞中CFTR和SLC26A6的表达。TGFβ诱导p38丝裂原活化蛋白激酶（MAPK）磷酸化，P38 MAPK抑制剂SB203580可逆转TGFβ诱导的CFTR和SLC26A6表达降低。
幽门螺杆菌感染通过TGFβ介导的P38 MAPK信号通路下调十二指肠上皮细胞CFTR和SLC26A6的表达，这有助于进一步阐明幽门螺杆菌相关十二指肠溃疡的发病机制。
The pathogenesis of Helicobacter pylori (H. pylori) infection-induced duodenal ulcer remains to be elucidated. Duodenal mucosal bicarbonate secretion is the most important protective factor against acid-induced mucosal injury. We previously revealed that H. pylori infection downregulated the expression and functional activity of duodenal mucosal cystic fibrosis transmembrane conductance regulator (CFTR) and solute linked carrier 26 gene family A6 (SLC26A6) which are the two key duodenal mucosal epithelial cellular bicarbonate transporters to mediate duodenal bicarbonate secretion. In this study, we investigated the mechanism of H. pylori infection-induced duodenal CFTR and SLC26A6 expression downregulation. We found that H. pylori infection induced the increase of serum transforming growth factor β (TGFβ) level and duodenal mucosal TGFβ expression and the decrease of duodenal mucosal CFTR and SLC26A6 expressions in C57 BL/6 mice. The results from the experiments of human duodenal epithelial cells (SCBN) showed that H. pylori increased TGFβ production and decreased CFTR and SLC26A6 expressions in SCBN cells. TGFβ inhibitor SB431542 reversed the H. pylori-induced CFTR and SLC26A6 expression decreases. The further results showed that TGFβ directly decreased CFTR and SLC26A6 expressions in SCBN cells. TGFβ induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and P38 MAPK inhibitor SB203580 reversed the TGFβ-induced CFTR and SLC26A6 expression decreases. H. pylori infection downregulates duodenal epithelial cellular CFTR and SLC26A6 expressions through TGFβ-mediated P38 MAPK signaling pathway, which contributes to further elucidating the pathogenesis of H. pylori-associated duodenal ulcer.
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影响因子：
3.7
作者：
Snodgrass SM;Cihil KM;Cornuet PK;Myerburg MM;Swiatecka-Urban A
通讯作者：
Swiatecka-Urban A
DOI：
10.1111/j.1748-1716.2010.02207.x
发表时间：
2011-01
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Dong X;Ko KH;Chow J;Tuo B;Barrett KE;Dong H
通讯作者：
Dong H
影响因子：
4.3
作者：
Graham, David Y.
通讯作者：
Graham, David Y.
影响因子：
5.7
作者：
Li N;Xie C;Lu NH
通讯作者：
Lu NH
影响因子：
4.3
作者：
Moyat, Mati;Velin, Dominique
通讯作者：
Velin, Dominique