Open Access
Hepatocyte aquaporins in bile formation and cholestasis
Raul Alberto Marinelli1,Guillermo Luis Lehmann1,Leandro Raul Soria1,Maria Julia Marchissio1
Instituto de Fisiologia Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, 2000 Rosario, Santa Fe, Argentina.
DOI: 10.2741/3877 Volume 16 Issue 7, pp.2642-2652
Published: 01 June 2011
(This article belongs to the Special Issue Experimental and clinical cholestasis)

Bile formation by hepatocytes is an osmotic secretory process that is ultimately dependent on the biliary secretion of osmotically-active solutes (mainly bile salts) via specialized canalicular transporters as well as on the water permeability of the canalicular plasma membrane domain. Hepatocytes express aquaporins, a family of membrane channel proteins that facilitate the osmotically-driven movement of water molecules. Aquaporin-8 (AQP8), localized to canalicular membranes, modulates membrane water permeability providing a molecular mechanism for the osmotically-coupled transport of solute and water during bile formation. There is experimental evidence suggesting that defective hepatocyte AQP8 expression leads to alterations in normal bile physiology. Thus, AQP8 protein is downregulated (and canalicular water permeability decreased), in established rat models of cholestasis, such as sepsis-associated cholestasis, estrogen-induced cholestasis and extrahepatic obstructive cholestasis. Moreover, AQP8 gene silencing in the human hepatocyte-derived cell line HepG2 inhibits canalicular water secretion. Based on current knowledge, it is conceivable that cholestasis results from a mutual occurrence of impaired solute transport and AQP8-mediated decrease of canalicular water permeability.

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Raul Alberto Marinelli, Guillermo Luis Lehmann, Leandro Raul Soria, Maria Julia Marchissio. Hepatocyte aquaporins in bile formation and cholestasis. Frontiers in Bioscience-Landmark. 2011. 16(7); 2642-2652.