microRNA profile changes match with proteome analysis during liver regeneration after rat partial hepatectomy

Introduction: The liver has the unique capacity to regenerate after surgical resection. However, the mechanisms of liver regeneration are not completely understood. Small non-coding microRNAs (miRNAs) have been shown play a critical role in regulation of hepatocyte proliferation during carcinogenesis, development and early regeneration. We hypothesized that miRNAs are involved in all phases of regeneration after liver resection.

Methods: We performed miRNA microarray analyses after 70% partial hepatectomy in Wistar rats (n=3) at six different time points (0, 2, 6, 12, 24, 48 hours, and 5 days). Putative targets of differentially expressed miRNAs were determined using a bioinformatic approach. 2D-PAGE proteomic analyses and protein identification were performed on specimens at 0 and 24 hours after resection. Standard parameters of liver regeneration (Brdu, PCNA, IL-6, HGF) were investigated to characterize the temporal dynamic of liver regeneration.

Results: miRNA expression patterns changed during all phases of liver regeneration. Most explicit changes were observed during the peak of DNA replication 24 hours after resection. Eleven miRNAs were significantly downregulated 12–48 hours after partial hepatectomy including miR-26a and four members of the let-7 family, whereas only two miRNAs were expressed at significantly higher levels (>25% change). Proteome analysis from three randomly chosen up-regulated spots revealed 16 proteins, mainly involved in cell metabolism, out of which one third represented putative targets of the differentially expressed miRNAs.

Discussion: We provide a temporal miRNA expression dataset of the regenerating rat liver, which indicates a primary function for miRNA during the peak of DNA replication. These data will assist further functional studies on the role of miRNAs during liver regeneration.

liver regeneration - miRNA - partial hepatectomy