UC Davis

BACKGROUND.: The molecular mechanisms underlying the growth of small size grafts and the remaining livers are poorly understood. MicroRNAs (miRNAs) negatively modulate expression of genes that are involved in cellular function and metabolism. The aim of this study is to identify critical miRNA species that modulate the growth of small grafts and the remaining livers after partial hepatectomy (PH). METHODS.: Small size graft liver transplantation was performed in rats. Liver tissue was harvested after transplant or PH for the determination of miRNA expression profile, and the data were confirmed by quantitative reverse-transcriptase polymerase chain reaction. The genes involved in cell cycle and proliferation were analyzed by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemical staining. RESULTS.: Compared with control liver, miR_122a, Let_7b, and miR_26a were reduced by more than 90% in 45% volume grafts. In the remaining livers after 50% PH, 30 miRNAs were down-regulated by more than 50%, and among them, miR_22a, miR_26a, miR_30b, Let_7f, and Let_7g were markedly decreased. A negative correlation existed between down-regulated miRNAs and highly up-regulated genes involved in cell cycle and proliferation in the remaining livers. Moreover, overexpression of miR_26a markedly down-regulated cyclin E2 protein levels and significantly decreased proliferation of HepG2 cells. CONCLUSION.: Down-regulated miRNAs play a pivotal role in promoting the growth of small size grafts and the remaining livers. The negative correlation between down-regulated miRNAs and up-regulated genes suggests that these specific miRNAs participate in the modulation of a growth response in both living donors and small size graft recipients.