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- Title
Overexpression of mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse.
- Authors
Kahraman, Alisan; Mott, Justin L.; Bronk, Steven F.; Werneburg, Nathan W.; Barreyro, Fernando J.; Guicciardi, Maria E.; Akazawa, Yuko; Braley, Karen; Craig, Ruth W.; Gores, Gregory J.
- 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.
- Subjects
FIBROSIS; CELL death; COLLAGEN diseases; HEPATOCYTE growth factor; LIVER cells; APOPTOSIS; CYTOKINES; LABORATORY mice
- Publication
Digestive Diseases & Sciences, 2009, Vol 54, Issue 9, p1908
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-008-0583-5