Expression and role of β-catenin in suppression of liver regeneration in small-for-size liver graft after transplantation in rats / 中华器官移植杂志

ABSTRACT

Objective To investigate the expression and role of β-catenin in small-for-size liver grafts during early stage of liver regeneration after liver transplantation in rats.Method The livers of male Sprague-Dawley rats were reduced to 30％ or 50％ of their original sizes and transplanted.The experiment was divided into 3 groupssmall-for-size graft group (SSG),half-size graft group (HSG) and sham-operated group.Liver samples were harvested at various time points after transplantation (n =6 per time point) for Western blotting and immunohistochemistry.Six rats in each group were sacrificed at 3rd day after liver transplantation for estimating liver regeneration rate.Result Liver regeneration rate in SSG group was lower than that in HSG group.The expression of β-catenin was down-regulated in liver graft of both groups after being stored in cold Ringer solution for 2 h.The expression of β-catenin was significant up-regulated in HSG group from 5 min to 12 h after operation,while the down-regulated expression of β-catenin was persisted in SSG group at 5 min after operation,and mildly increased expression of β-catenin occurred at 2 h and 6 h,which was significantly lower than that in HSG group at the corresponding time points.The expression of active-β-catenin was low in each group before transplantation.Significant expression of active-β-catenin was found at 5 min in HSG group and persisted until 12 h after operation,mildly increased expression of active-β-catenin in SSG group was only found at 2 h,which was lower than that in HSG group at the same time points.Immunohistochemical staining revealed that β-catenin was mainly expressed on the hepatocyte membrane and in cytoplasm in the sham-operative group,many hepatocytes exhibited nuclear localization of β-catenin in HSG group from 5 min to 24 h,while only some hepatocytes exhibited nuclear localization of β-catenin in SSG group.The expression of Cyclin D1 in SSG group was significantly lower than that in HSG group,which was similar to the expression of C-Myc.Conclusion Attenuated activation of Wnt/β-catenin signaling and down-regulated expression of target genes during early regeneration of small-for-size liver grafts may be involved in the inhibition of liver regeneration of small for size liver grafts.