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

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 6-72h. 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 remaining 6 via superior mesenteric vein. Three animals from each group were sacrificed at 24h and 7 days for liver assessment. RESULTS: AS group exhibited a significant decrease in total beta-catenin at 24h. A significant decrease in liver/body weight ratio was also observed in the AS group at 24h 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: Thus, we demonstrate 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.