Date Published: March 31, 2019
Publisher: Impact Journals
Author(s): Francesco Scavello, Filippo Zeni, Calogero C. Tedesco, Emanuela Mensà, Fabrizio Veglia, Antonio Domenico Procopio, Anna Rita Bonfigli, Fabiola Olivieri, Angela Raucci.
The receptor for advanced glycation end-products (RAGE) recognizes several ligands involved in inflammatory diseases. Two circulating soluble isoforms exist: esRAGE derived from alternative splicing and cRAGE generated by the membrane-bound RAGE (FL-RAGE) proteolysis. Together, esRAGE and cRAGE constitute sRAGE and function as decoy receptors preventing FL-RAGE/ligands binding.
The receptor for advanced glycation end-products (RAGE) belongs to the family of pattern recognition receptor (PRR) that recognizes several ligands, such as advanced glycation end-products (AGE), some S100/calgranulins, amyloid-beta peptide, High Mobility Group Box 1 protein (HMGB1) and extracellular matrix proteins [1,2].
In the present study, we analysed for the first time the circulating levels of different isoforms of soluble RAGE, i.e. cRAGE and esRAGE, in a cohort of healthy subjects aged 20-90 years-old, to investigate their age-related trends. We show that esRAGE, deriving from alternative splicing , does not vary during aging and eventually represents the predominant circulating sRAGE isoform in the elderly-old subjects (Fig. 1B). On the other hand, cRAGE, generated by proteolytic cleavage of FL-RAGE by ADAM10 and/or MMPs [24,26], is the most abundant circulating sRAGE in the young group and significantly decreases with advancing age dropping to very low if any levels in the elderly-old cohort (Fig. 1C). Therefore, the age-related decline of sRAGE in the blood is due to cRAGE changes (Fig.1). No significant gender differences were observed for both isoforms during aging, except for a significant higher concentration of sRAGE in the middle-age group of females compared to males ascribable to cRAGE variations (Fig. 3). Our data extend previously published data showing that in a general population sRAGE levels is slightly but significantly higher in middle-age women compared to men [38,39]. The reason for this is currently unknown, but estrogen levels may be involved [43,44].