Upregulation of NM23-E2 accelerates the liver regeneration after 40% decreased-size liver transplantation in rats

J Surg Res. 2017 Nov:219:325-333. doi: 10.1016/j.jss.2017.06.033. Epub 2017 Jul 22.

Abstract

Background: Potential of liver regeneration after living-donor liver transplantation is closely associated with the recipient's prognosis, whereas exogenous gene might regulate the liver regeneration progress. NM23 is a multifunctional gene, which inhibits tumor metastasis and regulates cell proliferation, differentiation, development, and apoptosis; however, there is little research about NM23 in promoting liver cell proliferation.

Methods: To investigate the effect of NM23-E2 on the liver cell proliferation, the NM23-E2 overexpression vector or negative control vector was transfected into BRL-3A cells and donor liver, respectively. NM23-E2, Cyclin D1, and PCNA expression levels in BRL-3A cells and liver tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Cell Counting Kit-8 was used to detect cell proliferation and flow cytometry for investigating cell cycle. The liver regeneration rate was determined by calculating (regenerated-liver weight of recipient - liver weight of donor/liver weight of donor) × 100%.

Results: NM23-E2 overexpression increased the NM23-E2, Cyclin D1, and PCNA levels significantly in BRL-3A cells and liver tissues (P < 0.05). The number of S phase cells was more than that of negative control group, and cell proliferation rate was higher than that of the control group in BRL-3A cells markedly (P < 0.05). Moreover, the liver regeneration rate in the NM23-E2 overexpression group was also higher than that in negative control group on postoperative day 1, day 3, day 5, and day 7.

Conclusions: Overexpression of NM23-E2 can increase Cyclin D1 and PCNA expression, shorten cell cycle, and thereby promoting the proliferation of liver cells and accelerating the regeneration of liver after 40% decreased-size rat liver transplantation.

Keywords: 40% decreased-size rat liver transplantation; BRL-3A cells; Liver regeneration; NM23-E2.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Genetic Therapy*
  • Lentivirus
  • Liver / metabolism
  • Liver Regeneration*
  • Liver Transplantation*
  • Male
  • NM23 Nucleoside Diphosphate Kinases / genetics*
  • NM23 Nucleoside Diphosphate Kinases / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats, Sprague-Dawley

Substances

  • NM23 Nucleoside Diphosphate Kinases
  • Proliferating Cell Nuclear Antigen
  • Cyclin D1