PMC:3897850 / 1069-3256 JSONTXT

{"project":"2_test","denotations":[{"id":"24465234-1378843-44839185","span":{"begin":139,"end":140},"obj":"1378843"},{"id":"24465234-7662668-44839186","span":{"begin":268,"end":269},"obj":"7662668"},{"id":"24465234-22750165-44839187","span":{"begin":536,"end":537},"obj":"22750165"},{"id":"24465234-23838007-44839188","span":{"begin":695,"end":696},"obj":"23838007"},{"id":"24465234-8256857-44839189","span":{"begin":801,"end":802},"obj":"8256857"},{"id":"24465234-8256857-44839190","span":{"begin":907,"end":908},"obj":"8256857"},{"id":"24465234-19477910-44839191","span":{"begin":910,"end":911},"obj":"19477910"},{"id":"24465234-24102034-44839192","span":{"begin":1077,"end":1078},"obj":"24102034"},{"id":"24465234-19404313-44839193","span":{"begin":1247,"end":1248},"obj":"19404313"},{"id":"24465234-22834835-44839194","span":{"begin":1557,"end":1558},"obj":"22834835"},{"id":"24465234-17566693-44839195","span":{"begin":1560,"end":1562},"obj":"17566693"},{"id":"24465234-24102034-44839196","span":{"begin":1739,"end":1740},"obj":"24102034"}],"text":"Introduction\nReceptor for advanced glycation endproducts (RAGE) is a transmembrane protein that belongs to the immunoglobulin superfamily [1]. As its name implicates, it can bind to advanced glycation endproducts, the resulting product of non-enzymatic glycosylation [2], and it also has the ability to interact with multiple ligands having common motifs as a so-called multi-ligand receptor. The ligands include high-mobility group protein (B)1 (HMGB1), S-100 calcium-binding protein, amyloid-β-protein, Mac-1, and phosphatidylserine [3]. Interaction between RAGE and its ligands activates various cellular processes, including inflammation, proliferation, apoptosis, autophagy, and migration [4]. Expression of RAGE is different, depending on the organ, developmental stage, and cellular condition [5]. It is highly expressed during the embryonic stage, whereas it is mostly kept at low levels in adults [5, 6]. Mostly, it is stimulated by cellular stresses, such as inflammation, and is therefore easily found to be abnormally over-expressed in many human chronic diseases [7]. Accumulation of advanced glycation endproducts (AGEs) is highly associated with the pathogenesis of diabetes, which causes serious consequences on metabolic systems [8]. In addition, expression of S100 proteins is reported to be involved in many cancers, including breast, lung, kidney, and thyroid cancers. Mostly, their up-regulation promotes tumorigenesis by stimulating metastasis through the activation of relevant transcription factors or by acting as chemoattractants [9, 10]. In addition to cancers, RAGE and its ligands are abnormally regulated in various types of chronic immune diseases, such as atherosclerosis, Alzheimer disease, and arthritis [7]. Increasing evidence demonstrates the critical role of RAGE signaling in many other human diseases and suggests its stimulating factors as potential biomarkers for diagnosis or therapy. In this review, we are going to summarize the RAGE signaling pathway and its contribution to the pathogenesis of human diseases, focused specifically on kidney diseases. Further, we propose the possibility of using RAGE and its ligands as therapeutic targets."}