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Updated: Jun 1, 2026

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Published on: October 9, 2014
Alternative splicing of RAGE: roles in biology and disease
Anastasia Z Kalea1, Ann Marie Schmidt, Barry I Hudson
1Division of Nephrology/Hypertension, Feinberg School of Medicine, Northwestern University, IL, USA.
Abstract:
The Receptor for Advanced Glycation End-products (RAGE) is a complex, multi-ligand signaling system implicated in the pathogenesis of diabetes, cardiovascular disease and various cancers. RAGE undergoes extensive alternative splicing to produce a variety of transcripts with diverse functions, including soluble antagonists and variants with altered ligand binding domains. Studies focused on the major soluble variant (RAGEv1/esRAGE) have revealed this to function by binding RAGE-ligands and preventing activation of RAGE signaling in vascular and tumor cells. Furthermore, measurement of this variant in human serum has revealed that RAGEv1/esRAGE levels may represent a novel biomarker for RAGE-ligand related pathogenic states. Understanding the full plethora of RAGE alternative splicing and its regulation is central to elucidating the role of RAGE in biology and disease.
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