Small interfering RNA targeting receptor for advanced glycation end products suppresses the generation of proinflammatory cytokines

摘要

The aim of the present study was to investigate the effect of receptor for advanced glycation end products (RAGE)-specific small interfering (si)RNA on the generation of proinflammatory cytokines in primary rat hepatic stellate cells (HSCs) and hepatic fibrotic (HF) rats. The RAGE-specific siRNA expression vector pAKD-GR126 was constructed, and then transfected into primary rat HSCs. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were conducted to determine the mRNA and protein expression levels, respectively, of RAGE, tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the primary HSCs. In addition, a CCl4-induced Sprague Dawley (SD) rat model of hepatic fibrosis was established, and pAKD-GR126 was injected into the SD rats via the tail vein. Serum TNF-α and IL-6 concentrations were determined using radioimmunoassay. The mRNA and protein expression levels of RAGE (mRNA, F=7.791; protein, F=36.513), TNF-α (mRNA, F=474.568; protein, F=123.500) and IL-6 (mRNA, F=203.463; protein, F=320.555) in the pAKD-GR126-transfected primary HSCs were significantly reduced compared with those in the control and pAKD-NC groups (P<0.05). Serum TNF-α and IL-6 levels in the low-, medium- and high-dose pAKD-GR126 treatment groups were reduced compared with those in the fibrotic model group (TNF-α, F=416.397; IL-6, F=1,716.659; P<0.05). In summary, the RAGE-specific siRNA was able to effectively suppress the generation of the proinflammatory cytokines TNF-α and IL-6 in primary rat HSCs and HF rats.