Foxl1 promotes liver repair following cholestatic injury in mice

Sara D. Sackett; Yan Gao; Soona Shin; Yonah B. Esterson; Akivaga Tsingalia; Reginald S. Hurtt; Karrie Brondell; Klaus H. Kaestner; Linda E. Greenbaum

doi:10.1038/labinvest.2009.103

Foxl1 promotes liver repair following cholestatic injury in mice

Sara D. Sackett, Yan Gao, Soona Shin, Yonah B. Esterson, Akivaga Tsingalia, Reginald S. Hurtt, Karrie Brondell, Klaus H. Kaestner, Linda E. Greenbaum

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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 Β-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/Β-catenin pathway.

Original language	English (US)
Pages (from-to)	1387-1396
Number of pages	10
Journal	Laboratory Investigation
Volume	89
Issue number	12
DOIs	https://doi.org/10.1038/labinvest.2009.103
State	Published - Dec 2009
Externally published	Yes

Keywords

B-catenin
Bile duct ligation
Cholangiocyte
Cyclin D1
Wnt

ASJC Scopus subject areas

Pathology and Forensic Medicine
Molecular Biology
Cell Biology

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10.1038/labinvest.2009.103

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title = "Foxl1 promotes liver repair following cholestatic injury in mice",

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 Β-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/Β-catenin pathway.",

keywords = "B-catenin, Bile duct ligation, Cholangiocyte, Cyclin D1, Wnt",

author = "Sackett, {Sara D.} and Yan Gao and Soona Shin and Esterson, {Yonah B.} and Akivaga Tsingalia and Hurtt, {Reginald S.} and Karrie Brondell and Kaestner, {Klaus H.} and Greenbaum, {Linda E.}",

note = "Funding Information: We thank Beth Helmbrecht, Tim Luo and Li-ya Yu for expert technical assistance, and Gary Swain and members of the University of Pennsylvania Center for Digestive Disease Morphology Core for their histology service. This study was supported by University of Pennsylvania Institute for Regenerative Medicine (to LEG and KHK), NIH Center Grant P-30-DK050306.",

year = "2009",

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doi = "10.1038/labinvest.2009.103",

language = "English (US)",

volume = "89",

pages = "1387--1396",

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AU - Sackett, Sara D.

AU - Gao, Yan

AU - Shin, Soona

AU - Esterson, Yonah B.

AU - Tsingalia, Akivaga

AU - Hurtt, Reginald S.

AU - Brondell, Karrie

AU - Kaestner, Klaus H.

AU - Greenbaum, Linda E.

N1 - Funding Information: We thank Beth Helmbrecht, Tim Luo and Li-ya Yu for expert technical assistance, and Gary Swain and members of the University of Pennsylvania Center for Digestive Disease Morphology Core for their histology service. This study was supported by University of Pennsylvania Institute for Regenerative Medicine (to LEG and KHK), NIH Center Grant P-30-DK050306.

PY - 2009/12

Y1 - 2009/12

N2 - 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 Β-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/Β-catenin pathway.

AB - 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 Β-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/Β-catenin pathway.

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KW - Cholangiocyte

KW - Cyclin D1

KW - Wnt

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Foxl1 promotes liver repair following cholestatic injury in mice

Abstract

Keywords

ASJC Scopus subject areas

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