title: Morpholino oligonucleotide-triggered beta-catenin knockdown compromises normal liver regeneration.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, School of Medicine, University of Pittsburgh, S421-BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
authors.forename: Dimple
authors.initials: D
authors.lastname: Sodhi
authors.forename: Amanda
authors.initials: A
authors.lastname: Micsenyi
authors.forename: William C
authors.initials: WC
authors.lastname: Bowen
authors.forename: Dulabh K
authors.initials: DK
authors.lastname: Monga
authors.forename: Juan-Carlos Lopez
authors.initials: JC
authors.lastname: Talavera
authors.forename: Satdarshan P S
authors.initials: SP
authors.lastname: Monga
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D060172:Morpholinos; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D055293:Receptors, Urokinase Plasminogen Activator; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D009025:Morpholines; D060172:Morpholinos; D016376:Oligonucleotides, Antisense; C524900:Plaur protein, rat; D016271:Proto-Oncogene Proteins c-myc; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019938:Cyclin D1