%0 Journal Article
%T Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases
%A Yaw Kuang Chuah
%A Rusliza Basir
%A Herni Talib
%A Tung Hing Tie
%A Norshariza Nordin
%J International Journal of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/403460
%X The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF- B as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions. 1. Introduction The receptor for advanced glycation end products (RAGE), which belongs to the immunoglobulin superfamily, was first identified and described in terms of its ability to bind advanced glycation end products (AGEs) [1, 2]. This explains the choice of ¡°RAGE¡± to name this receptor. Due to the ability of RAGE to recognize three-dimensional structures rather than specific amino acid sequences, RAGE is capable of engaging a diverse class of ligands that lack sequence similarities. Because of this feature, this multiligand receptor can therefore be considered a pattern-recognition receptor (PRR) [1, 3]. Ligands that have been found to be recognized by RAGE include AGEs [1], amyloid ¦Â-peptide [4], DNA binding protein high mobility group box-1 (HMGBl)/amphoterin [5], and S100/calgranulins [6]. In humans and mice, the gene encoding RAGE is located on chromosome 6 close to major histocompatibility complex III (MHC class III), in the vicinity of the genes for lymphotoxin, tumour necrosis factor (TNF), and the homeobox gene HOX12 [7, 8]. Translation of the mRNA transcribed from this human RAGE gene (~1.4£¿kb) results in a protein of 404 amino acids with a molecular mass of about 55£¿kDa [2]. RAGE is composed of a single hydrophobic transmembrane-spanning domain, a highly charged cytosolic tail, and an extracellular region (Figure 1). This extracellular region consists of one N-terminal V-type
%U http://www.hindawi.com/journals/iji/2013/403460/