Liver regeneration after partial hepatectomy: inconsistent results of expression screenings for human, mouse, and rat microRNAs.

TO THE EDITOR: Several recent studies investigated the role of microRNAs (miRNAs) in liver regeneration. These studies are typically based on microarray analyses of whole liver tissue, followed by quantitative real-time PCR or Northern blot confirmation. So far, nine studies have been published in this field (1– 4, 6, 7, 9 –11), of which five studies (1, 2, 7, 9, 11) show a similar design in regard to the degree of partial hepatectomy (70%), species (rats), time points (2 h up to 5 days), and controls (sham laparotomy). However, when comparing these five studies, we observed a relatively high discrepancy of their results. A total number of 72 miRNAs or miRNA families have been identified to be differentially expressed during liver regeneration. However, only three miRNAs (rno: let-7, miR-29a, miR93) show a consistent pattern of regulation in two independent studies at the same time point: whereas let-7 and miR-29a were found to be downregulated 24 h after partial hepatectomy, miR-93 was upregulated at 3 and 24 h postoperatively (1, 7, 9) (Table 1). Furthermore, upregulation has been described for four miRNAs [has/mmu-miR-106 (rno-miR-17–5p homolog), rno-miR-20b, rno-miR-21, rno-miR-365] by Castro et al. (1), which was not observed in any other study (2, 7, 9, 11). This lack of consistency may be caused by different time points for miRNA analyses. Further confounders such as drugs, feeding, or age may also explain these differences. Importantly, analyses have been performed in different species (human, mouse, or rat) microarray and quantitative RTPCR platforms. In this regard, Castro et al. (1) presented 26 miRNAs to be differentially expressed after partial hepatectomy, including 18 human, five murine, and three rat miRNAs. Although it is generally assumed that miRNAs are evolutionarily conserved among species, the mature sequence is not necessarily identical for miRNAs in different species (5), and some human or murine miRNAs have not yet been described in the rat. Unfortunately, for two human miRNAs (hsa-miR-573, hsa-miR-622) and for two murine miRNAs (mmu-miR-706, mmu-miR-720) described by Castro et al., rat homologs cannot Address for reprint requests and other correspondence: N. Raschzok, General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany (e-mail: nathanael. [email protected]).