Silencing of phospholipase C gamma 2 promotes proliferation of rat hepatocytes in vitro

The management of hepatic failure is undoubtedly difficult, and poor results have led to the search for novel therapeutic approaches. Nowadays, anti-apoptotic gene therapy is considered as an ideal approach. It has been proved that phospholipase C2 (PLC2) is involved in the apoptosis of immune cells and tumor cells; however, whether this gene is related to hepatocyte death is still unclear. This study examined the role of PLC2 by inhibiting its expression in rat hepatocytes with siRNA. We also further analyzed the cellular mechanism by which the expression inhibition of PLC2 induces cell death. Silencing PLC2 gene by adenovirus vector expressing PLC2-targeted siRNA caused the great decline in the number of G1- and G2/M phase cells, the significant increase in the number of S phase cells, and the obvious reduction in apoptosis index. In addition, silencing PLC2 gene relieved the rat hepatocyte damage, such as the cell shrinkage and chromatin condensation, nuclear fragmentation. Further analysis of Ad-PLC2 siRNA-transfected hepatocytes demonstrated that suppression of PLC2 gene expression could cause the caspase dependent cell death by inhibiting the signal pathway MEKK1/MKK4/JNK1/2/c-Jun. In conclusion, these findings suggest that interference with PLC2 expression could relieve the inhibitory effect of PLC2 on hepaocyte apoptosis, thus, promote proliferation through inactivating PKC-mediated JNK1/2 signaling pathway.