Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse

Alisan Kahraman; Justin L. Mott; Steven F. Bronk; Nathan W. Werneburg; Fernando J. Barreyro; Maria E. Guicciardi; Yuko Akazawa; Karen Braley; Ruth W. Craig; Gregory J. Gores

doi:10.1007/s10620-008-0583-5

Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse

Alisan Kahraman, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Fernando J. Barreyro, Maria E. Guicciardi, Yuko Akazawa, Karen Braley, Ruth W. Craig, Gregory J. Gores

Gastroenterology and Hepatology

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

7 Scopus citations

Abstract

Hepatocyte apoptosis contributes to liver injury and fibrosis after cholestatic injury. Our aim was to ascertain if the anti-apoptotic protein Mcl-1 alters liver injury or fibrosis in the bile duct-ligated mouse. Markers of apoptosis and fibrosis were compared in wild-type and transgenic mice expressing human Mcl-1 after bile duct ligation. Compared to hMcl-1 transgenic animals, ligated wild-type mice displayed a significant increase in TUNEL-positive cells and in caspase 3/7-positive hepatocytes. Consistent with apoptotic injury, the pro-apoptotic protein Bak underwent a conformational change to an activated form upon cholestatic injury, a change mitigated by hMcl-1 overexpression. Likewise, liver histology, number of bile infarcts, serum ALT values, markers of hepatic fibrosis, and animal survival were improved in bile duct-ligated mice transgenic for hMcl-1 as compared to wild-type mice. In conclusion, increased Mcl-1 expression plays a role in hepatoprotection upon cholestatic liver injury.

Original language	English (US)
Pages (from-to)	1908-1917
Number of pages	10
Journal	Digestive diseases and sciences
Volume	54
Issue number	9
DOIs	https://doi.org/10.1007/s10620-008-0583-5
State	Published - Sep 2009

Keywords

Apoptosis
Bile infarct
Liver fibrosis
Stellate cells

ASJC Scopus subject areas

Physiology
Gastroenterology

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10.1007/s10620-008-0583-5

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@article{98d8510381c74f3c94a16ffe846d9ea1,

title = "Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse",

abstract = "Hepatocyte apoptosis contributes to liver injury and fibrosis after cholestatic injury. Our aim was to ascertain if the anti-apoptotic protein Mcl-1 alters liver injury or fibrosis in the bile duct-ligated mouse. Markers of apoptosis and fibrosis were compared in wild-type and transgenic mice expressing human Mcl-1 after bile duct ligation. Compared to hMcl-1 transgenic animals, ligated wild-type mice displayed a significant increase in TUNEL-positive cells and in caspase 3/7-positive hepatocytes. Consistent with apoptotic injury, the pro-apoptotic protein Bak underwent a conformational change to an activated form upon cholestatic injury, a change mitigated by hMcl-1 overexpression. Likewise, liver histology, number of bile infarcts, serum ALT values, markers of hepatic fibrosis, and animal survival were improved in bile duct-ligated mice transgenic for hMcl-1 as compared to wild-type mice. In conclusion, increased Mcl-1 expression plays a role in hepatoprotection upon cholestatic liver injury.",

keywords = "Apoptosis, Bile infarct, Liver fibrosis, Stellate cells",

author = "Alisan Kahraman and Mott, {Justin L.} and Bronk, {Steven F.} and Werneburg, {Nathan W.} and Barreyro, {Fernando J.} and Guicciardi, {Maria E.} and Yuko Akazawa and Karen Braley and Craig, {Ruth W.} and Gores, {Gregory J.}",

note = "Funding Information: Acknowledgments This work was supported by a fellowship grant from the Association for Scientific Research and Science at the Department of Gastroenterology and Hepatology, University Clinic Essen, Duisburg-Essen University, 45122—Germany to A. K. and by Grant DK 41876 from the National Institute of Health to G. J. G., as well as the Mayo Foundation Rochester, Minnesota, USA. The authors thank Erin Nystuen-Bungum for her excellent secretarial assistance and James Tarara from the Division of Biochemistry and Molecular Biology (Mayo Clinic, Rochester, MN) for quantitation of the Sirius red images.",

year = "2009",

month = sep,

doi = "10.1007/s10620-008-0583-5",

language = "English (US)",

volume = "54",

pages = "1908--1917",

journal = "Digestive diseases and sciences",

issn = "0163-2116",

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T1 - Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse

AU - Kahraman, Alisan

AU - Mott, Justin L.

AU - Bronk, Steven F.

AU - Werneburg, Nathan W.

AU - Barreyro, Fernando J.

AU - Guicciardi, Maria E.

AU - Akazawa, Yuko

AU - Braley, Karen

AU - Craig, Ruth W.

AU - Gores, Gregory J.

N1 - Funding Information: Acknowledgments This work was supported by a fellowship grant from the Association for Scientific Research and Science at the Department of Gastroenterology and Hepatology, University Clinic Essen, Duisburg-Essen University, 45122—Germany to A. K. and by Grant DK 41876 from the National Institute of Health to G. J. G., as well as the Mayo Foundation Rochester, Minnesota, USA. The authors thank Erin Nystuen-Bungum for her excellent secretarial assistance and James Tarara from the Division of Biochemistry and Molecular Biology (Mayo Clinic, Rochester, MN) for quantitation of the Sirius red images.

PY - 2009/9

Y1 - 2009/9

N2 - Hepatocyte apoptosis contributes to liver injury and fibrosis after cholestatic injury. Our aim was to ascertain if the anti-apoptotic protein Mcl-1 alters liver injury or fibrosis in the bile duct-ligated mouse. Markers of apoptosis and fibrosis were compared in wild-type and transgenic mice expressing human Mcl-1 after bile duct ligation. Compared to hMcl-1 transgenic animals, ligated wild-type mice displayed a significant increase in TUNEL-positive cells and in caspase 3/7-positive hepatocytes. Consistent with apoptotic injury, the pro-apoptotic protein Bak underwent a conformational change to an activated form upon cholestatic injury, a change mitigated by hMcl-1 overexpression. Likewise, liver histology, number of bile infarcts, serum ALT values, markers of hepatic fibrosis, and animal survival were improved in bile duct-ligated mice transgenic for hMcl-1 as compared to wild-type mice. In conclusion, increased Mcl-1 expression plays a role in hepatoprotection upon cholestatic liver injury.

AB - Hepatocyte apoptosis contributes to liver injury and fibrosis after cholestatic injury. Our aim was to ascertain if the anti-apoptotic protein Mcl-1 alters liver injury or fibrosis in the bile duct-ligated mouse. Markers of apoptosis and fibrosis were compared in wild-type and transgenic mice expressing human Mcl-1 after bile duct ligation. Compared to hMcl-1 transgenic animals, ligated wild-type mice displayed a significant increase in TUNEL-positive cells and in caspase 3/7-positive hepatocytes. Consistent with apoptotic injury, the pro-apoptotic protein Bak underwent a conformational change to an activated form upon cholestatic injury, a change mitigated by hMcl-1 overexpression. Likewise, liver histology, number of bile infarcts, serum ALT values, markers of hepatic fibrosis, and animal survival were improved in bile duct-ligated mice transgenic for hMcl-1 as compared to wild-type mice. In conclusion, increased Mcl-1 expression plays a role in hepatoprotection upon cholestatic liver injury.

KW - Apoptosis

KW - Bile infarct

KW - Liver fibrosis

KW - Stellate cells

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IS - 9

ER -

Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse

Abstract

Keywords

ASJC Scopus subject areas

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