Cholestasis induces reversible accumulation of periplakin in mouse liver.
Cholestasis induces reversible accumulation of periplakin in mouse liver.
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DOI：
10.1186/1471-230x-13-116
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发表时间：
2013-07-13
影响因子：
2.4
通讯作者：
Gonzalez FJ
中科院分区：
文献类型：
--
作者：
Ito S;Satoh J;Matsubara T;Shah YM;Ahn SH;Anderson CR;Shan W;Peters JM;Gonzalez FJ
环链蛋白（PPL）是一种杆状细胞连接蛋白，被认为是连接细胞黏附连接复合物和细胞骨架细丝。PPL作为皮肤中凝固包膜的结构成分，并与培养细胞中各种类型的蛋白质相互作用；在人上皮组织的致瘤性进展过程中，其水平急剧下降。尽管有这些有趣的观察结果，但PPL的生理作用，特别是在非皮肤组织中的作用，在很大程度上仍然未知。由于我们观察到小鼠肝脏中PPL表达的显著波动与胆汁酸受体farnesoid X受体（FXR）和胆汁淤积有关，我们试图表征PPL在肝脏中的作用，并确定其对胆汁淤积的病因和发病机制的贡献。通过免疫组织化学、western blotting和定量实时聚合酶链反应检测各种肝脏和肾脏疾病小鼠模型中PPL的时间和环境依赖性表达。Fxr−/−小鼠肝脏PPL表达显著降低。相比之下，在胆汁淤积期间，PPL的表达急剧增加，在野生型小鼠的肝细胞边界处观察到大量PPL的积累。有趣的是，由胆汁淤积引起的PPL的肝脏积聚是可逆的。此外，输尿管梗阻时，在肾小管周围的上皮细胞中也发现了类似的PPL在细胞边界的积累。PPL可能参与不同组织对液瘀的时间调节。进一步研究PPL的作用可能会发现一种适用于许多组织和许多环境的细胞连接物保护细胞的新机制。
Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in non-cutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis. Time- and context-dependent expression of PPL in various mouse models of hepatic and renal disorders were examined by immunohistochemistry, western blotting, and quantitative real-time polymerase chain reactions. The hepatic expression of PPL was significantly decreased in Fxr−/− mice. In contrast, the expression was dramatically increased during cholestasis, with massive PPL accumulation observed at the boundaries of hepatocytes in wild-type mice. Interestingly, the hepatic accumulation of PPL resulting from cholestasis was reversible. In addition, similar accumulation of PPL at cellular boundaries was found in epithelial cells around renal tubules upon ureteral obstruction. PPL may be involved in the temporal accommodation to fluid stasis in different tissues. Further examination of the roles for PPL may lead to the discovery of a novel mechanism for cellular protection by cytolinkers that is applicable to many tissues and in many contexts.