Protective effect of RNA interference targeting Ikkß on hepatic fibrosis in rats.

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 ß (IKKß) complex. IKK ß is the key kinase in the NF-κB activation pathway. After inhibition, it can block the activation of NF-κB. IKKß 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 IKKß-siRNA lentivirus vector treatment for hepatic fibrosis of rats. An IKKß-siRNA expression plasmid was constructed and injected in the tail vein of rats. Then, IKKß-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. IKKß-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. IKKß-siRNA can be an effective method of anti-fibrosis gene therapy for liver fibrosis.