The Glycoform Modifications of sRAGE Matter

Abstract

Copyright: © 2013 Tae HJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The signaling of Receptors for Advanced Glycation End Products (RAGE) results in inflammation and tissue remodeling, and has been implicated in several human diseases, including cardiovascular disease [1-3]. Soluble RAGE (sRAGE) encompassing the entire ectoportion of RAGE, but lacking the membrane anchor and cytosolic signaling domain, functions as a decoy that counteracts RAGE-mediated inflammatory signaling by competing for RAGE ligands and dampening the subsequent inflammation and tissue remodeling [4]. RAGE/sRAGE is known to be modified by N-linked glycosylation at two locations of the ligand binding V ectodomain [5], and such modification has been shown to be important for RAGE bioactivity [6,7]. Recombinant sRAGE has been generated and tested in several disease models in mice [8-10] or rats [11], and the results have shown a promise for future clinical applications. However, in these studies, recombinant sRAGE was produced in the fall armyworm (Spodoptera frugiperda) cell line sf9 via a baculovirus vector [8-11], rather than in mammalian source, making immunogenicity as well as bioactivity an issue.