Specific siRNA Targeting the Receptor for Advanced Glycation End Products Inhibits Experimental Hepatic Fibrosis in Rats

Abstract

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-κB activity, hepatic stellate cell activation, and accumulation of extracellular matrix proteins in the fibrotic liver, and also greatly improved the histopathology and the ultra-structure of liver cells. These effects may be partially mediated by the inhibition on IκBα degradation. RAGE gene silencing effectively prevented liver from fibrosis, therefore it offers a potential pharmacological tool for anti-HF gene therapy.

Keywords

• Receptor for advanced glycation end products (RAGE)
• small interfering RNA (siRNA)
• hepatic stellate cells (HSCs)
• hepatic fibrosis (HF)
• gene therapy