Loss of α-catenin elicits a cholestatic response and impairs liver regeneration
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Herr-2014-Loss of a-catenin.pdf
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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
Date Issued
October 2014
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
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.
MIT 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
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DOI of Published Version
https://doi.org/10.1038/srep06835
