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Hepatocyte aquaporins in bile formation and cholestasis. | LitMetric

Hepatocyte aquaporins in bile formation and cholestasis.

Front Biosci (Landmark Ed)

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.

Published: June 2011

AI Article Synopsis

  • * Aquaporin-8 (AQP8) plays a crucial role in regulating how water moves through the canalicular membranes of hepatocytes, which is essential for bile production.
  • * Defective AQP8 expression has been linked to various forms of cholestasis, suggesting that a decrease in AQP8 reduces water permeability and disrupts normal bile flow.

Article Abstract

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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Source
http://dx.doi.org/10.2741/3877DOI Listing

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