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

J Cell Biochem. 2018 May;119(5):4085-4096. doi: 10.1002/jcb.26592. Epub 2018 Jan 22.


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 Cγ2 (PLCγ2) 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 PLCγ2 by inhibiting its expression in rat hepatocytes with siRNA. We also further analyzed the cellular mechanism by which the expression inhibition of PLCγ2 induces cell death. Silencing PLCγ2 gene by adenovirus vector expressing PLCγ2-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 PLCγ2 gene relieved the rat hepatocyte damage, such as the cell shrinkage and chromatin condensation, nuclear fragmentation. Further analysis of Ad-PLCγ2 siRNA-transfected hepatocytes demonstrated that suppression of PLCγ2 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 PLCγ2 expression could relieve the inhibitory effect of PLCγ2 on hepaocyte apoptosis, thus, promote proliferation through inactivating PKCδ-mediated JNK1/2 signaling pathway.

Keywords: PKCδ-JNK pathway; RNA interference; cell proliferation; phospholipase C gamma 2; rat hepatocyte; recombinant adenovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Cycle*
  • Gene Expression Regulation, Enzymologic*
  • Gene Silencing*
  • Hepatocytes / cytology
  • Hepatocytes / enzymology*
  • MAP Kinase Signaling System*
  • Phospholipase C gamma / biosynthesis*
  • Phospholipase C gamma / genetics
  • Rats
  • Rats, Sprague-Dawley


  • Phospholipase C gamma