Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice.
Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice.
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DOI：
10.1371/journal.pone.0117599
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Verkade HJ
中科院分区：
文献类型：
--
作者：
Bodewes FA;Bijvelds MJ;de Vries W;Baller JF;Gouw AS;de Jonge HR;Verkade HJ
囊性纤维化肝病（CFLD）的病因尚不清楚。众所周知，肝脏暴露于疏水胆汁盐与肝脏疾病的发展有关。因此，我们假设，在肝脏处理疏水胆盐时，CFTR依赖性变异与CFLD的发生有关。为了验证我们的假设，我们研究了Cftr-/-和对照小鼠在正常喂养条件下和在急性（静脉注射）或慢性（通过饮食三周）暴露期间的胆汁分泌、胆汁成分和肝脏病理。在Cftr-/-和对照小鼠中，基础胆汁产量相当。在Cftr-/-和对照小鼠中，静脉注射牛磺酸胆酸盐增加胆汁生成的程度相同。然而，慢性胆酸暴露对Cftr-/-小鼠的胆流量的增加明显低于对照组，同时Cftr-/-小鼠的胆盐浓度明显高于对照组。然而，在Cftr-/-小鼠中，长时间的胆碱暴露不会诱发CFLD样病理。慢性胆酸暴露确实诱导对照小鼠肝脏质量显著增加，而Cftr-/-小鼠则不存在这种情况。慢性胆酸盐给药诱导囊性纤维化特异性肝胆表型，包括胆汁成分的改变。这些变化不能像CF小鼠肝脏的病理改变一样与CFLD相关。然而，慢性胆酸盐给药诱导对照小鼠肝脏生长，而Cftr-/-小鼠则不存在这种情况。我们的研究结果指出，在CF条件下，长期暴露于疏水胆汁盐会损害肝脏的适应性同养性反应。
The cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous) or chronic (three weeks via the diet). In Cftr-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.
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影响因子：
13.5
作者：
Lindblad, A;Glaumann, H;Strandvik, B
通讯作者：
Strandvik, B
影响因子：
5
作者：
MASHIGE, F;IMAI, K;OSUGA, T
通讯作者：
OSUGA, T
DOI：
10.1152/ajpgi.00295.2004
发表时间：
2005-04-01
影响因子：
4.5
作者：
Bijvelds, MJC;Bronsveld, I;Verkade, HJ
通讯作者：
Verkade, HJ
影响因子：
15.9
作者：
FITZ, JG;BASAVAPPA, S;COHN, JA
通讯作者：
COHN, JA
影响因子：
5.2
作者：
Debray, Dominique;Kelly, Deirdre;Colombo, Carla
通讯作者：
Colombo, Carla