The Regulatory Role Of Proliferation And Apoptosis Of ERK1/2 And JNK Signaling Pathways In Eight Liver Cell Types During Rat Liver Regeneration

After rats were under partial hepatectomy (PH), the signal molecule promoted the remnant liver cells into the cell cycle in succession by activating signal transduction to promote transcription factors to transcript, replaced the lost liver cells and restored the physiological function of the liver, this process will be regulated and controlled by many signaling pathways including ERK1/2, JNK, etc. Some previous research reports almost focused on functions of unit genes in liver regeneration (LR) and were limited in organizations. But the liver is constituted by hepatocytes (HC), biliary epithelia cells (BEC), hepatic stellate cells (HSC), oval cells (OC), sinusoidal endothelial cells (SEC), Kupffer cells (KC), pit cells (PC), dendritic cells (DC) and so on. In order to understanding the functions of ERK1/2 and JNK signaling pathways on the eight kinds of cells of rat regenerating liver at the transcriptional level, the genes related ERK 1/2 and JNK signaling pathways were obtained according to NCBI, KEGG, QIAGEN and GENMAPP, etc. eight kinds of cells of rat regenerating liver were purified by percoll density gradient centrifugation and immunomagnetic bead method, the gene expression profiles of ERK1/2 and JNK signaling pathways were detected by the Rat Genome 230 2.0 microarray assay, and bioinformatics and systems biology methods to analyze the indicationg on physiological activities of the gene expression profiles above. The results are as follows:1. There are 14 pathways (named paths) and 165 genes were involved in the ERK1/2 signaling pathway, and 161 genes were included in Rat Genome 230 2.0 Array. Of them, 119 genes associated with liver regeneration. Synergy analysis of genes in ERK1/2 signaling pathway showed that, this signaling pathway started HC, HSC and KC activation in the priming phase of LR, promoted HC, BEC and HSC and some SEC and KC proliferation in the progressing phase, promoted SEC but weakened HC,OC,HSC,PCå'ŒDC proliferation in the terminal phase.2. There are 42 paths and 302 genes were involved in the JNK signaling pathway, and 240 genes were included in Rat Genome 230 2.0 Array. Of them, 225 genes associated with liver regeneration. Synergy analysis of genes in JNK signaling pathway showed that, in the priming phase of LR, this signaling pathway promoted DC apoptosis at the priming phase of LR, promoted HC, DC and PC proliferation in the priming and progressing phase, promoted OC apoptosis in the priming and terminal phase, promoted KC proliferation and PC apoptosis in the whole LR, and showed a larger difference of regulatory of proliferation and apoptosis on HSC and SEC in the three different phase of LR.In summary, 11 paths and 119 genes of ERK 1/2 signaling pathway regulated cell proliferation, and 42 paths and 225 genes of JNK signaling pathway regulated cell proliferation and apoptosis. in eight rat regenerating liver cell types.