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.