Specific siRNA targeting the receptor for advanced glycation end products inhibits experimental hepatic fibrosis in rats.
Receptor for advanced glycation end products (RAGE) was studied in different stages of carbon tetrachloride induced hepatic fibrosis (HF), and effect of its gene silencing in the HF development was evaluated in rats. Silencing RAGE expression by specific siRNA effectively suppressed NF-kappaB activity, hepatic stellate cell activation, and accumulation of extracellular matrix proteins in the fibrotic liver, and also greatly improved the histopathology and the ultrastructure of liver cells. These effects may be partially mediated by the inhibition on IkappaBalpha degradation. RAGE gene silencing effectively prevented liver from fibrosis, therefore it offers a potential pharmacological tool for anti-HF gene therapy.
Xia
Jin-Rong
JR
Department of Gastroenterology, Zhong Da Hospital, Southeast University, Nanjing 210009, China.
Liu
Nai-Feng
NF
Department of Gastroenterology, Zhong Da Hospital, Southeast University, Nanjing 210009, China.
Zhu
Nai-Xun
NX
Department of Gastroenterology, Zhong Da Hospital, Southeast University, Nanjing 210009, China.