Foxl1 promotes liver repair following cholestatic injury in mice.
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 beta-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/beta-catenin pathway.
Sackett
Sara D
SD
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, USA.
Gao
Yan
Y
Shin
Soona
S
Esterson
Yonah B
YB
Tsingalia
Akivaga
A
Hurtt
Reginald S
RS
Brondell
Karrie
K
Kaestner
Klaus H
KH
Greenbaum
Linda E
LE
D000818:Animals; D049109:Cell Proliferation; D002779:Cholestasis / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008026:Ligation; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism
D051858:Forkhead Transcription Factors; C099993:Foxl1 protein, mouse; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C095937:Wnt7b protein, mouse; D051176:beta Catenin; D019938:Cyclin D1