Wnt signaling plays a central role in many processes during hepatic development and in adult liver homeostasis. Two distinct Wnt signaling pathways, the canonical and the non-canonical pathway, have been described. Since the canonical Wnt/?-catenin activation during liver regeneration has been previously identified and it has been demonstrated that non-canonical Wnt pathways can antagonize the Wnt/?-catenin pathway, we decided to study the involvement of non-canonical Wnt during the process of liver regeneration. We used a model of 2/3rd partial hepatectomy (PH) in C57BL/6 mice, where after PH, three mice were sacrificed at 1, 2, 3, 7, 14 days and livers were harvested for paraffin embedding, protein and RNA analysis. qPCR analysis shows an increase in the expression of Wnt5a mRNA by 2- and 2.6-fold after 24 and 48 hours, respectively. Fzd2 expression increases by around 2- and 3-fold at 48 and 72 hours respectively, in PH samples vs sham controls. Despite modulation of Wnt5a and Fzd2, Western Blot analysis failed to show any significant differences in the activation of downstream PKC and CamKII kinases. In hepatocarcinoma cell lines Hep3B and HepG2, Wnt5a inhibits the transcriptional activity of beta-catenin. Thus, Wnt5a may be involved in negatively regulating the Wnt/?-catenin signaling and thus modulating hepatocyte proliferation during the liver regeneration through as yet unidentified mechanism.
Non-canonical Wnt signaling during liver regeneration
Cusimano Antonella;
2011
Abstract
Wnt signaling plays a central role in many processes during hepatic development and in adult liver homeostasis. Two distinct Wnt signaling pathways, the canonical and the non-canonical pathway, have been described. Since the canonical Wnt/?-catenin activation during liver regeneration has been previously identified and it has been demonstrated that non-canonical Wnt pathways can antagonize the Wnt/?-catenin pathway, we decided to study the involvement of non-canonical Wnt during the process of liver regeneration. We used a model of 2/3rd partial hepatectomy (PH) in C57BL/6 mice, where after PH, three mice were sacrificed at 1, 2, 3, 7, 14 days and livers were harvested for paraffin embedding, protein and RNA analysis. qPCR analysis shows an increase in the expression of Wnt5a mRNA by 2- and 2.6-fold after 24 and 48 hours, respectively. Fzd2 expression increases by around 2- and 3-fold at 48 and 72 hours respectively, in PH samples vs sham controls. Despite modulation of Wnt5a and Fzd2, Western Blot analysis failed to show any significant differences in the activation of downstream PKC and CamKII kinases. In hepatocarcinoma cell lines Hep3B and HepG2, Wnt5a inhibits the transcriptional activity of beta-catenin. Thus, Wnt5a may be involved in negatively regulating the Wnt/?-catenin signaling and thus modulating hepatocyte proliferation during the liver regeneration through as yet unidentified mechanism.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
