PLC2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD/JNK MAPK and PKCD/p38 MAPK signalling

ObjectivesThe PLCG2 (PLC2) gene is a member of PLC gene family encoding transmembrane signalling enzymes involved in various biological processes including cell proliferation and apoptosis. Our earlier study indicated that PLC2 may be involved in the termination of regeneration of the liver which is mainly composed of hepatocytes, but its exact biological function and molecular mechanism in liver regeneration termination remains unclear. This study aims to examine the role of PLC2 in the growth of hepatocytes. Materials and methodsA recombinant adenovirus expressing PLC2 was used to infect primary rat hepatocytes. PLC2 mRNA and protein levels were detected by qRT-PCR and Western blot. The subcellular location of PLC2 protein was tested by an immunofluorescence assay. The proliferation of hepatocytes was measured by MTT assay. The cell cycle and apoptosis were analysed by flow cytometry. Caspase-3, -8 and -9 activities were measured by a spectrophotometry method. Phosphorylation levels of PKCD, JNK and p38 in the infected cells were detected by Western blot. The possible mechanism underlying the role of PLC2 in hepatocyte growth was also explored by adding a signalling pathway inhibitor. ResultsHepatocyte proliferation was dramatically reduced, while cell apoptosis was remarkably increased. The results demonstrated that PLC2 increased the phosphorylation of PKCD, p38 and JNK in rat hepatocytes. After PKCD activity was inhibited by the inhibitor Go 6983, the levels of both p-p38 and p-JNK MAPKs significantly decreased, and PLC2-induced cell proliferation inhibition and cell apoptosis were obviously reversed. ConclusionsThis study showed that PLC2 regulates hepatocyte growth through PKCD-dependently activating p38 MAPK and JNK MAPK pathways; this result was experimentally based on the further exploration of the effect of PLC2 on hepatocyte growth in vivo.