title: Small interfering RNA targeting receptor for advanced glycation end products suppresses the generation of proinflammatory cytokines.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Langxi Chinese Medicine Hospital, Langxi, Anhui 242100, P.R. China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Cai
keywords: inflammation inhibition; interleukin-6; receptor for advanced glycation end products; small interfering RNA; tumor necrosis factor-α