Cholesterol gallstone Claudin Epithelial Barrier Paracellular permeability Phosphate gallstone Phosphate ion Tight junction
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摘要

BACKGROUND & AIMS:Most cholesterol gallstones have a core consisting of inorganic and/or organic calcium salts, although the mechanisms of core formation are poorly understood. We examined whether the paracellular permeability of ions at hepatic tight junctions is involved in the core formation of cholesterol gallstones, with particular interest in the role of phosphate ion, a common food additive and preservative.
METHODS:We focused on claudin-3 (Cldn3), a paracellular barrier-forming tight junction protein whose expression in mouse liver decreases with age. Since Cldn3-knockout mice exhibited gallstone diseases, we used them to assess the causal relationship between paracellular phosphate ion permeability and the core formation of cholesterol gallstones.
RESULTS:In the liver of Cldn3-knockout mice, the paracellular phosphate ion permeability through hepatic tight junctions was significantly increased, resulting in calcium phosphate core formation. Cholesterol overdose caused cholesterol gallstone disease in these mice.
CONCLUSION:We revealed that in the hepatobiliary system, Cldn3 functions as a paracellular barrier for phosphate ions, to help maintain biliary ion homeostasis. We provide in vivo evidence that elevated phosphate ion concentrations play a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease under cholesterol overdose.
LAY SUMMARY:Herein, we reveal a new mechanism for cholesterol gallstone formation, in which increased paracellular phosphate ion permeability across hepatobiliary epithelia causes calcium phosphate core formation and cholesterol gallstones. Thus, altered phosphate ion metabolism under cholesterol overdose plays a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease.

译文

背景与目的: 大多数胆固醇结石的核心由无机和/或有机钙盐组成,尽管核心形成的机制知之甚少。我们检查了肝紧密连接处离子的细胞旁通透性是否与胆固醇结石的核心形成有关,特别关注磷酸盐离子的作用,磷酸盐离子是一种常见的食品添加剂和防腐剂。
方法: 我们关注 claudin-3 (Cldn3),一种细胞旁屏障形成紧密连接蛋白,其在小鼠肝脏中的表达随着年龄的增长而减少。由于 Cldn3-knockout 小鼠表现出胆结石疾病,我们用它们来评估细胞旁磷酸盐离子通透性和胆固醇胆结石核心形成之间的因果关系。
结果: 在 Cldn3-knockout 小鼠肝脏中,通过肝紧密连接的细胞旁磷酸盐离子通透性明显增加,导致磷酸钙核心形成。胆固醇过量导致这些小鼠胆固醇结石病。
结论: 我们揭示了在肝胆系统中,Cldn3 作为磷酸离子的细胞旁屏障,有助于维持胆汁离子稳态。我们提供了体内证据,证明磷酸盐离子浓度升高在胆固醇过量导致胆固醇结石病的生活方式和年龄相关风险中起主要作用。
总结: 在此,我们揭示了胆固醇结石形成的一种新机制,即肝细胞上皮细胞旁磷酸盐离子通透性增加导致钙磷酸盐核心形成和胆固醇结石。因此,在胆固醇过量的情况下,磷酸离子代谢的改变在发展胆固醇胆结石疾病的生活方式和年龄相关风险中起着重要作用。

gallstone

消化 肝胆系统疾病 疾病
概述  :  

胆结石,又称胆石症,是发生于肝胆系统内任何部位的结石,包括胆囊结石、胆总管结石、肝总管结石、肝内胆管结石、复合部位结石等,属于消化系统常见疾病,结石反复刺激可引起炎症及胆道梗阻,从而出现腹痛、发烧、黄疸、呕吐等症状,严重者还可能出现感染休克,危及生命安全。 流行病学胆结石的发病率在不同国家、不同人种之间都存在差异。可能与遗传因有关。不同国家间胆结石的类型也存在差异。在西方国家,75%以上的胆结石为胆固醇型,通常发生在胆囊内;在非洲和亚洲,以胆色素结石为主并多见于胆管内。生活方式如饮

gallstone 英 /ˈɡɔːlstəʊn/  美 /ˈɡɔːlstoʊn/

释义   n. 胆石;胆结石

例句   Gallstone:Mass of crystallized substances that forms in the gallbladder. 胆石:在胆囊形成的大量晶体化物质。


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