Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration.

In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (Et) according to their expression profiles. The results showed that the Et values of G protein-coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.

Meta-analysis of epidemiological studies of association of two polymorphisms in the interleukin-10 gene promoter and colorectal cancer risk.

In order to make a comprehensive assessment of the potential association between two genetic variants in the IL-10 gene promoter, -1082 A>G (rs1800896) and -592 C>A (rs1800872), and colorectal cancer (CRC) risk, we conduced a meta-analysis of seven epidemiological studies, which included 1469 colorectal cancer cases and 2566 controls. Neither of the two polymorphisms had any association with increased CRC risk in overall population [for rs1800896: odds ratio (OR) = 0.90, 95% confidence interval (95%CI) = 0.76-1.06 in the dominant model and for rs1800872: OR = 1.06, 95%CI = 0.91-1.23 in the dominant model]. In subgroup analysis of the rs1800896 polymorphism, the results did not change when the analyses were restricted to individual studies, or those fulfilling Hardy-Weinberg equilibrium, or according to the source of controls. For rs1800872, however, when stratifying by the source of controls, the A allele had a significant increased risk of CRC among studies with population-based controls in the codominant model (AC vs CC: OR = 1.30, 95%CI = 1.04-1.63) and dominant model (AA/AC vs CC: OR = 1.25, 95% CI = 1.01-1.55). Based on this meta-analysis, we conclude that the IL-10 rs1800872 polymorphism could be a risk factor for CRC development among European populations. However, we found no association between the IL-10 rs1800896 polymorphism and CRC risk. Further studies, either with larger sample size or involving other SNPs and haplotypes of the IL-10 gene, are necessary to clarify the contribution of IL-10 genetic variations in colorectal carcinogenesis.