1. ¹Department of Genetics, Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
2. ²Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Correspondence: Dr LE Greenbaum, MD, Department of Cancer Biology and Medicine, Thomas Jefferson University, 233 S 10th Street, 306 BLSB, Philadelphia, PA 19107, USA. E-mail: linda.greenbaum@jefferson.edu

³These authors contributed equally to this work.

^*Current Address: Medizinische Klinik II, Universitatsklinikum Aachen, Aachen, Germany.

Received 29 May 2009; Revised 10 August 2009; Accepted 17 August 2009; Published online 19 October 2009.

Abstract

Cholangiocyte proliferation is one of the hallmarks of the response to cholestatic injury. We previously reported that the winged helix transcription factor Foxl1 is dramatically induced in cholangiocytes following bile duct ligation. In this study, we investigated the function of Foxl1 in the bile duct ligation model of cholestatic liver injury in Foxl1^-/- and control mice. We found that Foxl1^-/- livers exhibit an increase in parenchymal necrosis, significantly impaired cholangiocyte and hepatocyte proliferation, and failure to expand bile ductular mass. Wnt3a and Wnt7b expression was decreased in the livers of Foxl1^-/- mice along with reduced expression of the -catenin target gene Cyclin D1 in Foxl1^-/- cholangiocytes. These results show that Foxl1 promotes liver repair after bile-duct-ligation-induced liver injury through activation of the canonical wnt/-catenin pathway.