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

Author(s)
Herr, Keira Joann; Tsang, Ying-hung Nicole; Ong, Joanne Wei En; Li, Qiushi; Yap, Lai Lai; Yu, Weimiao; Yin, Hao; Dahlman, James E.; Chan, Yee Gek; Bay, Boon Huat; Singaraja, Roshni; Kotelianski, Victor E.; Viasnoff, Virgile; Thiery, Jean Paul; Bogorad, Roman; Anderson, Daniel Griffith; ... Show more Show less
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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.
Date issued
2014-10
URI
http://hdl.handle.net/1721.1/92572
Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Herr, Keira Joann, Ying-hung Nicole Tsang, Joanne Wei En Ong, Qiushi Li, Lai Lai Yap, Weimiao Yu, Hao Yin, et al. “Loss of α-Catenin Elicits a Cholestatic Response and Impairs Liver Regeneration.” Sci. Rep. 4 (October 30, 2014): 6835.
Version: Final published version
ISSN
2045-2322

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