Function and expression of cystic fibrosis transmembrane conductance regulator after small intestinal transplantation in mice.

Function and expression of cystic fibrosis transmembrane conductance regulator after small intestinal transplantation in mice.
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小鼠小肠移植后囊性纤维化跨膜电导调节因子的功能及表达

DOI:
10.1371/journal.pone.0062536
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zheng S
Zheng S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Song P;Song W;Liu X;Jin C;Xie H;Zhou L;Tuo B;Zheng S

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移植物的分泌功能是肠道移植成功的重要因素之一。囊性纤维化跨膜电导调节因子(CFTR)介导肠上皮细胞HCO3-和Cl-的分泌。本研究以小鼠小肠移植为实验模型,对CFTR基因的表达和功能进行了研究。同种异体小鼠进行异位小肠移植。实时荧光定量聚合酶链式反应和蛋白印迹分析CFTRmRNA和蛋白的表达。用pH恒定和短路电流(ISC)技术,在Ussing小室中测定了小鼠肠粘膜HCO3-和Cl2-的分泌。结果表明,异位空肠移植小鼠空肠粘膜上皮细胞分泌HCO_3~-和Cl~-明显低于对照组(P&lt;0.001),而异位空肠移植后供受者空肠粘膜上皮细胞分泌HCO_3~-和Cl~-明显低于对照组(P<0.05)。供体和受体小鼠空肠粘膜CFTRmRNA和蛋白表达水平均显著低于对照组(P&lt;0.001),肿瘤坏死因子αα表达水平显著高于对照组(P&lt;0.001)。进一步的实验表明,肿瘤坏死因子α下调了小鼠空肠粘膜CFTRmRNA的表达。结论:肠移植后CFTRmRNA和蛋白表达下调,可能是由肿瘤坏死因子α诱导的。
The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR) mediates HCO3 - and Cl- secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3 - and Cl- secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (Isc) techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3 - and Cl- secretions in mice, but forskolin-stimulated HCO3 - and Cl- secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001). The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001), and the mRNA and protein expression levels of tumor necrosis factor α (TNFα) were markedly increased in donor jejunal mucosae of mice (P<0.001), compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα.
DOI: 10.1136/gut.45.2.191
发表时间: 1999-08-01
期刊: GUT
影响因子: 24.5
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影响因子: 4.5
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