What is the role of the receptor for advanced glycation end products-ligand axis in liver injury?

Abstract

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 Receptor for advanced glycation end products (RAGE) is a multiligand-binding member of the immunoglobulin superfamily of cell surface molecules.1 The full-length receptor consists of an extracellular region formed from 1 V-type immunoglobulin domain needed for ligand binding and 2 C-type immunoglobulin domains; these domains are followed by a single, short transmembrane domain and a short cytoplasmic domain that is essential for RAGE-mediated signal transduction.

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease

“…AGEs and/or RAGE have been shown to be elevated in patients and experimental models of liver diseases [14,49,50,51,52]. Accordingly, we showed an increase in liver AGE content in HFD-fed rats.…”

Prognostic significance of receptor for advanced glycation end products expression in hepatocellular carcinoma after hepatectomy

“…These data suggest the organ-specific interaction of RAGE in tumor progression. Some literature reports the role of RAGE on various types of liver diseases, such as chronic hepatitis and liver cirrhosis [31,32], in eliciting oxidative stress generation and a subsequent inflammatory response that prolong inflammation and apoptosis. On the other hand, RAGE blockade attenuated tissue damage in hepatic ischemiaereperfusion injury and acetaminophen-induced hepatotoxicity in mice [33,34].…”

Advanced glycation end product (AGE)-induced hepatic stellate cell activation via autophagy contributes to hepatitis C-related fibrosis

“…Blocking RAGE attenuates HSC activation and autophagy induction RAGE, receptor of AGEs, is physiologically highly expressed in lung and pathologically expressed in the setting of diabetes, aging, inflammation, neurodegeneration, and tumors; however, its role in HCV-related liver fibrosis remains controversial [27]. In our current attempt, the RAGE expression data were used to delineate its role in HSC activation and proliferation.…”