William R Hunt1, Beth R Helfman2, Nael A McCarty2, Jason M Hansen3. 1. Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, GA, USA; Emory+Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: randy.hunt@emory.edu. 2. Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Emory University, Atlanta, GA, USA; Emory+Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA. 3. Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, USA.
Abstract
BACKGROUND: The onset of cystic fibrosis-related diabetes (CFRD) exacerbates lung function decline and increases mortality. One pathway that may worsen the lung dysfunction associated with CFRD is that of the receptor for advanced glycation end products (RAGE) and its ligands. METHODS: Human plasma was obtained from age-matched healthy, CF and CFRD patients. Plasma RAGE ligands (i.e. advanced glycation end products, S100A12, and high-mobility group protein B1) and soluble RAGE (sRAGE) levels were measured. RESULTS: CFRD patients had elevated plasma levels of AGEs and S100A12. Soluble RAGE, a RAGE ligand decoy receptor, was not significantly different between groups. Plasma AGE levels and S100A12 levels had significantly negative correlations with FEV1. CONCLUSIONS: AGEs are significantly elevated in CFRD and correlate negatively with FEV1. CFRD patients did not have significant increases in the decoy sRAGE, suggesting there may be heightened binding and activation of RAGE in CFRD exacerbating activation of proinflammatory pathways.
BACKGROUND: The onset of cystic fibrosis-related diabetes (CFRD) exacerbates lung function decline and increases mortality. One pathway that may worsen the lung dysfunction associated with CFRD is that of the receptor for advanced glycation end products (RAGE) and its ligands. METHODS:Human plasma was obtained from age-matched healthy, CF and CFRD patients. Plasma RAGE ligands (i.e. advanced glycation end products, S100A12, and high-mobility group protein B1) and soluble RAGE (sRAGE) levels were measured. RESULTS: CFRD patients had elevated plasma levels of AGEs and S100A12. Soluble RAGE, a RAGE ligand decoy receptor, was not significantly different between groups. Plasma AGE levels and S100A12 levels had significantly negative correlations with FEV1. CONCLUSIONS: AGEs are significantly elevated in CFRD and correlate negatively with FEV1. CFRD patients did not have significant increases in the decoy sRAGE, suggesting there may be heightened binding and activation of RAGE in CFRD exacerbating activation of proinflammatory pathways.
Authors: Rafał Rzepka; Barbara Dołęgowska; Aleksandra Rajewska; Daria Sałata; Marta Budkowska; Sebastian Kwiatkowski; Andrzej Torbé Journal: Biomed Res Int Date: 2016-07-31 Impact factor: 3.411
Authors: Charles D Bengtson; Michael D Kim; Abeer Anabtawi; Jianghua He; John S Dennis; Sara Miller; Makoto Yoshida; Nathalie Baumlin; Matthias Salathe Journal: Eur Respir J Date: 2021-01-14 Impact factor: 16.671