Dysregulated Bile Transporters and Impaired Tight Junctions During Chronic Liver Injury in Mice.
Dysregulated Bile Transporters and Impaired Tight Junctions During Chronic Liver Injury in Mice.
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DOI：
10.1053/j.gastro.2018.06.048
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发表时间：
2018-10
期刊：
影响因子：
29.4
通讯作者：
Sundd P
中科院分区：
文献类型：
--
作者：
Pradhan-Sundd T;Vats R;Russell JO;Singh S;Michael AA;Molina L;Kakar S;Cornuet P;Poddar M;Watkins SC;Nejak-Bowen KN;Monga SP;Sundd P
肝纤维化、肝细胞坏死、炎症和肝祖细胞增殖是慢性肝损伤的特征。小鼠模型已用于研究慢性肝损伤的终末期病理生理学。然而，由于我们无法观察小鼠体内肝损伤的进展情况，因此对不同小鼠模型之间肝损伤机制的差异知之甚少。我们开发了一种可视化活体小鼠胆汁运输和血胆屏障（BB1B）完整性的方法。 C57BL/6 小鼠被喂食缺乏胆碱的乙硫氨酸 (CDE) 饮食或含有 0.1% 3, 5-二乙氧基羰基-1, 4-二氢可力丁 (DDC) 的饮食长达 4 周，以诱导慢性肝损伤。我们使用定量肝脏活体显微镜 (qLIM) 实时评估喂食 CDE、DDC 或饲料（对照）饮食的活体小鼠完整肝脏中的胆汁运输和血胆屏障 (BB1B) 完整性。从小鼠身上收集肝组织，并通过组织学、免疫组织化学、实时 PCR 和免疫印迹进行分析。通过 qLIM 观察到，与对照小鼠相比，由 CDE 或 DDC 饮食引起的肝损伤小鼠的 BBlB 出现破裂，胆汁分泌受损。胆汁分泌受损与几种紧密连接蛋白（紧密连接蛋白 3、5 和 7）和胆汁转运蛋白（NTCP、OATP1、BSEP、ABCG5 和 ABCG8）的表达减少有关。延长（两周）CDE而非DDC饮食导致紧密连接蛋白和胆汁转运蛋白的重新表达，同时重建BBlB完整性和胆汁分泌。我们使用 qLIM 研究由缺乏胆碱或 DDC 饮食引起的小鼠慢性肝损伤。慢性肝损伤的进展伴随着胆汁转运蛋白和紧密连接蛋白的丧失。
Liver fibrosis, hepatocellular necrosis, inflammation and proliferation of liver progenitor cells are features of chronic liver injury. Mouse models have been used to study the end-stage pathophysiology of chronic liver injury. However, little is known about differences in the mechanisms of liver injury among different mouse models, due to our inability to visualize the progression of liver injury in vivo in mice. We developed a method to visualize bile transport and blood-bile barrier (BBlB) integrity in live mice. C57BL/6 mice were fed a choline-deficient ethionine supplemented (CDE) diet or a diet containing 0.1% 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) for up to 4 weeks to induce chronic liver injury. We used quantitative liver intravital microscopy (qLIM) for real-time assessment of bile transport and blood-bile barrier (BBlB) integrity in the intact livers of the live mice fed the CDE, DDC, or chow (control) diets. Liver tissues were collected from mice and analyzed by histology, immunohistochemistry, real-time PCR, and immunoblots. Mice with liver injury induced by a CDE or a DDC diet had breaches in the BBlB and impaired bile secretion, observed by qLIM compared to control mice. Impaired bile secretion was associated with reduced expression of several tight-junction proteins (claudins 3, 5, and 7) and bile transporters (NTCP, OATP1, BSEP, ABCG5 and ABCG8). A prolonged (two weeks) CDE but not DDC diet, led to re-expression of tight-junction proteins as well as bile transporters, concomitant to the reestablishment of BBlB integrity and bile secretion. We used qLIM to study chronic liver injury, induced by a choline-deficient or DDC diet, in mice. Progression of chronic liver injury was accompanied by loss of bile transporters and tight-junction proteins.
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影响因子：
29.4
作者：
Luedde T;Kaplowitz N;Schwabe RF
通讯作者：
Schwabe RF
影响因子：
6
作者：
Fickert, Peter;Stoeger, Ulrike;Trauner, Michael
通讯作者：
Trauner, Michael
影响因子：
5.9
作者：
Fox, Rena K.
通讯作者：
Fox, Rena K.
DOI：
10.1016/s0307-4412(00)00002-9
发表时间：
2000-05-01
期刊：
BIOCHEMICAL EDUCATION
影响因子：
--
作者：
Massou, S;Albigot, R;Prats, M
通讯作者：
Prats, M
影响因子：
13.5
作者：
Akhurst, B;Croager, EJ;Yeoh, GC
通讯作者：
Yeoh, GC