1. Loss of α-catenin elicits a cholestatic response and impairs liver regeneration.
- Author
-
Keira Joann Herr, Ying-hung Nicole Tsang, Joanne Wei En Ong, Qiushi Li, Lai Lai Yap, Weimiao Yu, Hao Yin, Bogorad, Roman L., Dahlman, James E., Yee Gek Chan, Boon Huat Bay, Singaraja, Roshni, Anderson, Daniel G., Koteliansky, Victor, Viasnoff, Virgile, and Thiery, Jean Paul
- Subjects
LIVER regeneration ,CATENINS ,LIVER disease treatment ,LIVER cells ,CELL communication ,CELL size ,CELL proliferation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF