What Is the Role of the Receptor for Advanced Glycation End Products-Ligand Axis in Liver Injury?

Multiligand receptor for advanced glycation end products (RAGE) is expressed in a wide variety of tissues, including the liver. Interactions with its ligands lead to cellular activation and thus prolonged inflammation and apoptosis. RAGE also exists in a soluble, truncated isoform called soluble RAGE, which has the same ligand-binding specificity as membrane-RAGE; acting as decoy, it can contribute to the removal/neutralization of circulating ligands and the resultant reduction of signaling pathway activation. Experimental and clinical studies have highlighted the idea that the RAGE-ligand axis is involved in the development of liver fibrosis, inflammation, and regeneration after a massive injury and in the setting of liver transplantation. The involvement of the RAGE-ligand axis in vascular disease, diabetes, cancer, and neurodegeneration is well established, but it still needs to be clarified in the setting of liver diseases. We present a review of the recent literature on this receptor in surgical and clinical settings involving the liver, and we highlight the open issues and possible directions of future research. Liver Transpl 17:633-640,2011. (C) 2011 AASLD.