Digestive diseases and sciences
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.
Animals, Apoptosis, Bile Ducts, Biological Markers, Cholestasis, Intrahepatic, Fibrosis, Hepatocytes, Humans, Ligation, Liver, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myeloid Cell Leukemia Sequence 1 Protein, Proto-Oncogene Proteins c-bcl-2
Kahraman, Alisan; Mott, Justin L.; Bronk, Steven F.; Werneburg, Nathan W.; Barreyro, Fernando J.; Guicciardi, Maria E.; Akazawa, Yuko; Braley, Karen; Craig, Ruth W.; and Gores, Gregory J., "Overexpression of mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse." (2009). Journal Articles: Biochemistry & Molecular Biology. 10.