MicroRNA profiling in murine liver after partial hepatectomy

Abstract

Abstract. Liver is uniquely capable to repair itself after injury. Multiple molecular and biochemical processes initiated after partial hepatectomy, lead to proliferation of all cells within the liver. MicroRNAs (miRNAs) are a class of highly abundant non-coding RNA molecules that cause post-transcriptional gene repression and are involved in several biological processes including cell cycle regulation and differentiation. In this study, we examined the expression levels of miRNAs in liver tissue received from control mice (L0) and compared them with the corresponding levels in liver tissue 12 h after liver regeneration induced by 2/3 partial hepatectomy (L12). MiRNA expression was investigated using microRNA profiling. Further qPCR analysis was used for validation of the differentially expressed miRNAs at an early stage of liver regeneration, induced by 2/3 partial hepatectomy. TargetScan and Gene Ontology (GO) analyses were performed in order to identify the possible miRNA target genes and their ontology, respectively. A subset of miRNAs was found to be differentially expressed during liver regeneration. Mmu-miR-21 and mmu-miR-30b * showed the higher levels of up-regulation in liver tissue from the hepatectomized mice at the end of the experiment (L12) compared to the sham operated mice (L0). Mmu-miR-21 up-regulation was further confirmed by qPCR. In situ hybridization (ISH) revealed that mmu-miR-21 exhibited the higher levels of expression at 12 h post hepatectomy. On the contrary, mmu-miR-34c * , mmu-miR-144, mmu-miR-207, mmu-miR-207, mmu-miR-451, mmu-miR-582-3p and mmu-miR-290-5p exhibited <0.5 downregulation in liver tissue after partial hepatectomy in L12 vs. L0 mice. The results from microarray and qPCR analyses were in good agreement. In conclusion, our results provide important information regarding the differentially expressed miRNAs in murine liver tissue before and after partial hepatectomy. The early up-regulation of mmu-miR-21 during the process of liver regeneration suggests a regulatory role in liver regeneration in vivo. IntroductionPartial hepatectomy (PH) represents the most commonly used model for the study of liver regeneration. It is a very complex and well-orchestrated phenomenon that is carried out by the participation of all mature liver cell types. The extent of hepatocyte proliferation is directly proportional to the amount of resected liver tissue and 2/3 partial hepatectomy (2/3 PH) leads to a highly synchronized hepatocyte cell-cycle entry and progression. The first phase, known as the 'priming phase', occurs in the first hours after PH and poises the hepatocytes to enter the G1 phase and to become receptive to growth factors. The second phase corresponds to an increased metabolic demand imposed on the remnant liver. During this phase, among other metabolic changes, transient hypoglycemia is suggested to induce systemic lipolysis followed by a lipid droplets accumulation in the hepatocytes. Between 36-42 h after 2/3 PH, most hepatocytes are in the S phase of the cell cycle. The rem...

MicroRNA-Gene Expression Network in Murine Liver during Schistosoma japonicum Infection

“…However, several miRNAs, such as mmu-miR-146b, mmu-miR-155, mmu-miR-223, mmu-miR-142-3p, mmu-miR-15b, and mmu-miR-126-5p, were observed to be up-regulated significantly in the mid-phase of infection (30 dpi) (Table 2 and Figure 3). Intriguingly, some of these miRNAs have been characterized to be associated with inflammation responses or the expression of oncogenes [28], [29]. More importantly, miR-155, miR-146, and miR-223 have been suggested to regulate the inflammatory responses after the recognition of pathogens by the Toll-like receptors (TLRs) [30], [31].…”

Study of MicroRNAs Related to the Liver Regeneration of the Whitespotted Bamboo Shark,Chiloscyllium plagiosum

“…The targets that were functionally annotated in the GO database could be divided to 38 subclasses, presented in Figure 4. Forty-six miRNAs were related to cell proliferation and growth terms (Supplementary Table 3), including the following miRNAs: xtr-miR-34a_R-1 [28], fru-miR-122_R+1 [29], fru-miR-27b_R-1 [30], fru-miR-181b_R+1 [31], fru-miR-23b_R-1 [32], ola-miR-144_L-1R+2_1ss12TA [33], ola-miR-103_R+2 [29], and fru-miR-26 [34]. Based on comprehensive consideration of our literature search, the small RNA sequencing results, miRNA target gene results, and GO analysis, three known miRNAs (hsa-miR-142-3p_R-1, xtr-miR-125b, and fru-miR-204) related to liver regeneration and liver diseases were screened to the following experiments, and the potential binding sites between miRNAs and the ESTs of Chiloscyllium plagiosum with miRanda were presented in Figure 5.…”

Dynamic recruitment of microRNAs to their mRNA targets in the regenerating liver

“…An essential contribution of miRNAs in this regenerative response has been supported by a recent study in which mice with genetic deletion of the DROSHA cofactor DGCR8, a factor required for microRNA biogenesis, exhibited markedly impaired hepatocyte proliferation after partial hepatectomy [17]. Although changes in expression of miRNAs after partial hepatectomy and in liver-graft models have been reported using array-based assays [17-24], only a small number of targets have been validated [22,23,25,26]. Importantly, the identification of the subset of mRNAs that are regulated by miRNAs in the regenerating liver is far from complete, in part due to the large number of possible mRNA:miRNA targeting relationships predicted by computational approaches.…”