title: Inhibitory effect of receptor for advanced glycation end product‑specific small interfering RNAs on the development of hepatic fibrosis in primary rat hepatic stellate cells.
abstract: Specific small interfering RNAs (siRNAs) targeting receptor for advanced glycation end products (RAGE) inhibit the expression of RAGE, α-smooth muscle actin and type I collagen in the T6 hepatic stellate cells (HSCs), indicating that RAGE is important for the activation of HSCs and the expression of collagen. The present study aimed to investigate the effect of specific siRNAs targeting RAGE on the development of hepatic fibrosis (HF), using primary rat HSCs, which were isolated and cultured in vitro. The expression vectors for specific siRNAs targeting RAGE were constructed and transfected into primary rat HSCs. Untreated and nonspecific siRNA-transfected primary rat HSCs served as controls. The expression levels of RAGE, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), laminin (LN), hyaluronic acid (HA) and N-terminal procollagen III propeptide (PIIINP) in primary HSCs were detected by reverse transcription quantitative polymerase chain reaction and western blotting. The mRNA and 42 kD protein expression of RAGE in the pAKD-GR126-transfected primary HSCs were significantly downregulated compared with those in the untreated and the pAKD-negative control (NC)-transfected controls. The mRNA and protein expression levels of IL-6, TNF-α, TGF-β1, CTGF, LN, HA and PIIINP in the pAKD-GR126-transfected primary HSCs were also markedly downregulated compared with those in the untreated and pAKD-NC-transfected controls. Therefore, RAGE-specific siRNAs inhibited the expression of RAGE in primary rat HSCs and inhibited the development of HF.
authors: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors: Jin-Rong
authors: JR
authors: Xia
authors: Department of Gastroenterology, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China.
authors: Ting-Ting
authors: TT
authors: Chen
authors: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors: Wei-Dong
authors: WD
authors: Li
authors: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors: Feng-Lin
authors: FL
authors: Lu
authors: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors: Juan
authors: J
authors: Liu
authors: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors: Xiao-Gang
authors: XG
authors: Cai
authors: Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors: Qin
authors: Q
authors: Lu
authors: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai 200080, P.R. China.
authors: Cui-Ping
authors: CP
authors: Yang
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000199:Actins; D024042:Collagen Type I; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; C000593874:Ager protein, rat; C498862:Acta2 protein, rat