Herr, Keira JoannTsang, Ying-hung NicoleOng, Joanne Wei EnLi, QiushiYap, Lai LaiYu, WeimiaoYin, HaoBogorad, Roman L.Dahlman, James E.Chan, Yee GekBay, Boon HuatSingaraja, RoshniAnderson, DanielKoteliansky, VictorViasnoff, VirgileThiery, Jean Paul2014-11-032014Herr, K. J., Y. N. Tsang, J. W. E. Ong, Q. Li, L. L. Yap, W. Yu, H. Yin, et al. 2014. “Loss of α-catenin elicits a cholestatic response and impairs liver regeneration.” Scientific Reports 4 (1): 6835. doi:10.1038/srep06835. http://dx.doi.org/10.1038/srep06835.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:13347611The 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.en-USJournal Article2014-11-0310.1038/srep06835