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Mitochondria are closely associated with cell survival, and it is of interest to determine whether apoptosis pathways, which are mediated by mitochondria, are involved in liver regeneration (LR). To identify the mechanisms underlying mitochondria-mediated apoptosis during rat LR, we used the Rat Genome 230 2.0 Array to investigate changes in gene expression. Next, we searched the GO and NCBI databases for genes associated with apoptosis mediated by mitochondria, and QIAGEN and KEGG databases for any related signaling pathways. The expression profile function (Et) was then used to calculate the activity level of known signaling pathways associated with apoptosis. The results revealed the expression of 436 genes associated with apoptosis signaling pathways, among which 152 were confirmed to be primarily related to LR. Overall, 99, 136, 95, and 91 genes were first expressed during the initiation [0.5-4 h after partial hepatectomy (PH)], G0/G1 transition (4-6 h after PH), cell proliferation (6-66 h after PH), and redifferentiation and structural reconstruction (66-144 h after PH) phases, demonstrating that LR-related genes were primarily induced in the initiation phase, and were then expressed across multiple phases. Analysis using the gene synergy formula (Et) showed that caspase-dependent and DNA fragment-related/unrelated pathways induced apoptosis in the early and late periods of LR, and the caspase-independent and DNA fragment-related/unrelated pathways almost in the whole process. Therefore, these results show that several apoptosis pathways regulate LR in rat.

Expression profiles of genes associated with mitochondria-mediated apoptosis and their roles in liver regeneration