Loss of α-catenin elicits a cholestatic response and impairs liver regeneration

Loss of α-catenin elicits a cholestatic response and impairs liver regeneration
Title:
Loss of α-catenin elicits a cholestatic response and impairs liver regeneration
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Scientific Reports
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Publication Date:
30 October 2014
Citation:
Scientific Reports 4, Article number: 6835 (2014)
Abstract:
The liver is unique in its capacity to regenerate after injury, during which hepatocytes actively divide and establish cell-cell contacts through cell adhesion complexes. Here, we demonstrate that the loss of α-catenin, a well-established adhesion component, dramatically disrupts liver regeneration. Using a partial hepatectomy model, we show that regenerated livers from α-catenin knockdown mice are grossly larger than control regenerated livers, with an increase in cell size and proliferation. This increased proliferation correlated with increased YAP activation, implicating α-catenin in the Hippo/YAP pathway. Additionally, α-catenin knockdown mice exhibited a phenotype reminiscent of clinical cholestasis, with drastically altered bile canaliculi, elevated levels of bile components and signs of jaundice and inflammation. The disrupted regenerative capacity is a result of actin cytoskeletal disorganisation, leading to a loss of apical microvilli, dilated lumens in the bile canaliculi, and leaky tight junctions. This study illuminates a novel, essential role for α-catenin in liver regeneration.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
Description:
ISSN:
2045-2322
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