Document Type

Article

Journal Title

Digestive diseases and sciences

Publication Date

9-2009

Volume

54

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.

MeSH Headings

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

ISSN

1573-2568

Comments

The final publication is available at Springer via 10.1007/s10620-008-0583-5

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