ABSTRACT
Generally, extra-cellular-signal-regulated kinase 5 (ERK5) signaling pathway regulates many physiological activities, such as cell proliferation and cell differentiation. However, little is known about how ERK5 signaling pathway composed of 15 paths participates in regulating hepatocyte proliferation during liver regeneration (LR). In this study, to explore the influence ERK5 signaling pathway upon hepatocytes at gene transcription level, rat genome 230 2.0 array was used to detect expression changes of 75 related genes in isolated hepatocytes from rat regenerating liver. Bioinformatics and systems biology methods were applied to analyze the precise role of ERK5 signaling pathway in regulating hepatocyte proliferation during LR. Results showed that 62 genes were contained in the array and 22 genes were significantly changed. It was found that 6 paths were related to hepatocyte proliferation during rat LR. Among them, paths 3, 6 and 13 of ERK5 signaling pathway modulated cell cycle progression by decreasing the negative influence on ERK5 and paths 3, 4, 8 and 9 by reinforcing the positive influence on ERK5. In summary, the study shows that 22 genes and 6 paths of ERK5 signaling pathway participate in regulating proliferation of hepatocytes in rat LR.
Subject(s)
Animals , Cell Growth Processes/genetics , Cell Growth Processes/physiology , Gene Expression Profiling/methods , Hepatectomy , Hepatocytes/cytology , Hepatocytes/enzymology , Hepatocytes/physiology , Liver Regeneration/genetics , Liver Regeneration/physiology , MAP Kinase Signaling System/genetics , MAP Kinase Signaling System/physiology , Mitogen-Activated Protein Kinase 7/genetics , Mitogen-Activated Protein Kinase 7/metabolism , Oligonucleotide Array Sequence Analysis/methods , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
Rapidly proliferating tissue may require enhanced DNA repair capacity in order to avoid fixation of promutagenic DNA lesions to mutations. Partial hepatectomy (PH) triggers cell proliferation during liver regeneration (LR). However, little is known on how DNA repair genes change and how they are regulated at the transcriptional level during LR. In the present study, the Rat Genome 230 2.0 array was used to detect the expression profiles of DNA repair genes during LR, and differential expression of selected genes was confirmed by real-time RT-PCR. 69 DNA repair genes were found to be associated with LR, more than half of which distributed in a cluster characterized by a gradual increase at 24-72h and then returning to normal. The expression of base excision repair- and transcription-coupled repair-related genes was enhanced in the early and intermediate phases of LR, whereas the expression of genes related to HR, NHEJ and DNA cross-link repair, as well as DNA polymerases and related accessory factors, and editing or processing nucleases, were mainly enhanced in the intermediate phase. The expression changes of genes in DNA damage response were complicated throughout the whole LR. Our data also suggest that the expression of most DNA repair genes may be regulated by the cell cycle during LR.