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J Hepatol. 2005 Jul;43(1):132-41. Epub 2005 Apr 25.

Morpholino oligonucleotide-triggered beta-catenin knockdown compromises normal liver regeneration.

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  • 1Department of Pathology, School of Medicine, University of Pittsburgh, S421-BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA.

Abstract

BACKGROUND/AIMS:

Wnt/beta-catenin activation is seen during early liver regeneration (LR) observed as stabilization and translocation to the nucleus followed by an overall decrease. However, beta-catenin continues to be in hepatocyte nucleus and membrane, secondary to its increased gene expression at 6-72 h.

METHODS:

In the present study, we examined the effect of ablating beta-catenin transcription on LR. Twelve male fisher rats were subjected to two-third partial hepatectomy followed by administration of beta-catenin antisense phospho-morpholino oligonucleotide (AS) in six or mismatch control (CON) injection in the remaining 6 via superior mesenteric vein. Three animals from each group were sacrificed at 24 h and 7 days for liver assessment.

RESULTS:

AS group exhibited a significant decrease in total beta-catenin at 24 h. A significant decrease in liver/body weight ratio was also observed in the AS group at 24 h and 7 days that was due to decreased proliferation. Among the targets of this pathway c-myc and uPAR levels showed significant decrease while cyclin-D1 remained unaffected.

CONCLUSIONS:

We demonstrate the importance of beta-catenin in early liver regeneration especially in hepatocyte proliferation. Also, c-myc and uPAR might be crucial downstream effectors of beta-catenin during liver regeneration.

PMID:
15893845
[PubMed - indexed for MEDLINE]
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