Role of receptor for advanced glycation end products (RAGE) in liver disease

Receptor for advanced glycation end products (RAGE) belongs to a immunoglobulin superfamily of cell surface molecules that could bind to a number of ligands such as advanced glycation end products, high-mobility group protein box-1, S-100 calcium-binding protein, and amyloid-β-protein, inducing a series of signal transduction cascades, and being involved in a variety of cellular function, including inflammation, proliferation, apoptosis, angiogenesis, migration, and fibrosis. RAGE is expressed in hepatic stellate cells and hepatocytes and hepatoma cells. There is accumulating evidence that engagement of RAGE with various ligands elicits oxidative stress generation and subsequently activates the RAGE downstream pathway in the liver, thereby contributing to the development and progression of numerous types of hepatic disorders. These observations suggest that inhibition of the RAGE signaling pathway could be a novel therapeutic target for liver diseases. This article summarizes the pathological role of RAGE in hepatic insulin resistance, steatosis and fibrosis, ischemic and non-ischemic liver injury, and hepatocellular carcinoma growth and metastasis and its therapeutic interventions for these devastating disorders.