Abstract
Objective. The importance of signal transduction in cell activities has been generally accepted. The purpose of this study was to analyze the regulatory effect of intracellular signaling cascade-associated genes on rat liver regeneration (LR) at transcriptional level. Material and methods. The associated genes were originally obtained through a search of the databases and related scientific publications; their expression profiles were then checked in rat LR using the Rat Genome 230 2.0 array. The LR-associated genes were identified by comparing the discrepancy in gene expression changes between the partial hepatectomy (PH) group and the sham operation (SO) group. Results. A total of 566 genes associated with the intracellular signaling cascade were LR related. The genes involved in nine signaling pathways including intracellular receptor-, second messenger-, nitric oxide-, hormone-, carbohydrate-mediated, protein kinase, small GTPase, ER-nuclear and target of rapamycin (TOR) signaling pathways were detected to be enriched in a cluster characterized by up-regulated expression in LR. According to their expression similarity and time relevance, they were separately classified into 5 and 5 groups. Conclusions. It is presumed that following PH, the second messenger-mediated signaling pathway inhibits the inflammatory response, while the protein kinase cascade and small GTPase-mediated signal transduction stimulate the immune response; the intracellular receptor-, second messenger-, small GTPase-mediated signal transduction and protein kinase cascade coordinately control cell replication; the intracellular receptor-, second messenger-mediated and ER-nuclear signaling pathways facilitate cell differentiation; the MAPK cascade and small GTPase-mediated signal transduction play a role in cytoskeletal reconstruction and cell migration; the second messenger-, small GTPase-mediated and IκB kinase/NFκB cascades take care of protein transport, etc., in LR.
Highlights
Liver is unique in its ability to regenerate rapidly even in adulthood [1]
According to the information from databases such as NCBI, AMIGO, BIOCARTA, KEGG, RGD and MGI, etc., 2417 genes were involved in the intracellular signaling cascade
110, 426, 15, 9, 2, 738, 369, 26 and 3 genes related to intracellular receptor, second messenger, nitric oxide, hormone, carbohydrate-mediated, protein kinase, small GTPase, ER-nuclear and target of rapamycin (TOR) signaling pathways were found in the Rat Genome 230 2.0 array
Summary
Liver regeneration (LR) is a process during which the liver recovers its mass and function after damage due to various causes such as partial hepatectomy (PH), virus infection and intoxication [1] This regenerative process is divided into four phases including the forepart (0.5Á4 h after PH), prophase (6Á12 h after PH), metaphase (16Á 66 h after PH) and the anaphase (72Á168 h after PH) according to time-course [2], and involves a series of complex physiological and biochemical activities which include cell activation, de-differentiation, proliferation and its regulation, and redifferentiation [3]. Based on the above data, their expression dynamics, interactions and actions during hepatic regeneration were further analyzed
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