Protective effect of RNA interference targeting Ikkβ on hepatic fibrosis in rats

J Cell Biochem. 2019 Nov;120(11):18894-18900. doi: 10.1002/jcb.29209. Epub 2019 Jul 11.

Abstract

Nuclear factor-κB (NF-κB) is an important regulatory factor in cells. NF-κB has a wide range of biological activities. After activation, it participates in the transcription and regulation of many genes and plays a role in infection, inflammatory response, oxidative stress, cell multiplication, and apoptosis. The activation of the NF-κB signal pathway is dependent on the degradation of the IκB kinase β (IKKβ) complex. IKK β is the key kinase in the NF-κB activation pathway. After inhibition, it can block the activation of NF-κB. IKKβ is a key regulator of NF-κB activation, also an early regulator of inflammation in all stages of the immune response. This study aimed to investigate the effect of IKKβ-siRNA lentivirus vector treatment for hepatic fibrosis of rats. An IKKβ-siRNA expression plasmid was constructed and injected in the tail vein of rats. Then, IKKβ-siRNA distribution in the liver was observed by immunofluorescence, and the quantitative polymerase chain reaction was used to detect inflammation-related and fibrosis-related factors. IKKβ-siRNA lentiviruses could be delivered to the liver and significantly decrease carbon tetrachloride-induced hepatic fibrosis. Furthermore, serum transaminase levels significantly decreased, and inflammation-related and fibrosis-related factors decreased. IKKβ-siRNA can be an effective method of anti-fibrosis gene therapy for liver fibrosis.

Keywords: IκB kinase β; RNAi; Rat liver fibrosis; lentivirus.

MeSH terms

  • Animals
  • Carbon Tetrachloride Poisoning / genetics
  • Carbon Tetrachloride Poisoning / metabolism
  • Carbon Tetrachloride Poisoning / pathology
  • Carbon Tetrachloride Poisoning / prevention & control
  • Genetic Vectors
  • I-kappa B Kinase* / antagonists & inhibitors
  • I-kappa B Kinase* / genetics
  • I-kappa B Kinase* / metabolism
  • Lentivirus
  • Liver Cirrhosis* / genetics
  • Liver Cirrhosis* / metabolism
  • Liver Cirrhosis* / pathology
  • Liver Cirrhosis* / prevention & control
  • Male
  • RNA Interference*
  • RNA, Small Interfering / biosynthesis
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Transduction, Genetic

Substances

  • RNA, Small Interfering
  • I-kappa B Kinase
  • Ikbkb protein, rat