scholarly journals Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury

2009 ◽  
Vol 297 (1) ◽  
pp. L1-L5 ◽  
Author(s):  
Xiao Su ◽  
Mark R. Looney ◽  
Naveen Gupta ◽  
Michael A. Matthay
Keyword(s):  
Lung Injury ◽  
Advanced Glycation End Products ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Experimental Models ◽  
Alveolar Type ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Receptor for advanced glycation end-products (RAGE) is a marker of alveolar type I cells and is elevated in the pulmonary edema fluid of patients with acute lung injury (ALI). We tested the hypothesis that RAGE in the bronchoalveolar lavage (BAL) would be elevated in experimental models of direct ALI characterized by alveolar epithelial cell injury. We developed ELISA measurements for RAGE and studied ALI (direct and indirect) mouse models and collected BAL at specified endpoints to measure RAGE. We also tested whether levels of BAL RAGE correlated 1) with the severity of lung injury in acid and hyperoxia-induced ALI and 2) with the beneficial effect of a novel treatment, mesenchymal stem cells (MSC), in LPS-induced ALI. In ALI models of direct lung injury induced by intratracheal instillation of acid, LPS, or Escherichia coli, the BAL RAGE was 58-, 22-, and 13-fold elevated, respectively. In contrast, BAL RAGE was not detectable in indirect models of ALI induced by an intraperitoneal injection of thiourea or by an intravenous injection of MHC I monoclonal antibody that produces a mouse model of transfusion-related ALI. BAL RAGE did correlate with the severity of lung injury in acid and hyperoxia-induced ALI. In addition, with LPS-induced ALI, BAL RAGE was markedly reduced with MSC treatment. In summary, BAL RAGE is an indicator of ALI, and it may be useful in distinguishing direct from indirect models of ALI as well as assessing the response to specific therapies.

scholarly journals Receptor for Advanced Glycation End-Products Is a Marker of Type I Cell Injury in Acute Lung Injury

2006 ◽  
Vol 173 (9) ◽  
pp. 1008-1015 ◽  
Author(s):  
Tokujiro Uchida ◽  
Madoka Shirasawa ◽  
Lorraine B. Ware ◽  
Katsuo Kojima ◽  
Yutaka Hata ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Advanced Glycation End Products ◽  
Cell Injury ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals The Receptor for Advanced Glycation End Products (RAGE) and the Lung

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Stephen T. Buckley ◽  
Carsten Ehrhardt
Keyword(s):  
Advanced Glycation End Products ◽  
Cell Injury ◽  
Immunoglobulin Superfamily ◽  
Alveolar Type ◽  
Exact Nature ◽  
Type I ◽  
Advanced Glycation ◽  
Diverse Range ◽  
Glycation End Products ◽  
End Products

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

scholarly journals Prothrombin is a binding partner of the human receptor of advanced glycation end products

2020 ◽  
Vol 295 (35) ◽  
pp. 12498-12511
Author(s):  
Genny Degani ◽  
Alessandra Altomare ◽  
Stefania Digiovanni ◽  
Beatrice Arosio ◽  
Guenter Fritz ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Calcium Binding ◽  
Transmembrane Helix ◽  
Alveolar Type ◽  
Type I ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Gla Domain

The receptor for advanced glycation end products (RAGE) plays a key role in mammal physiology and in the etiology and progression of inflammatory and oxidative stress-based diseases. In adults, RAGE expression is normally high only in the lung where the protein concentrates in the basal membrane of alveolar Type I epithelial cells. In diseases, RAGE levels increase in the affected tissues and sustain chronic inflammation. RAGE exists as a membrane glycoprotein with an ectodomain, a transmembrane helix, and a short carboxyl-terminal tail, or as a soluble ectodomain that acts as a decoy receptor (sRAGE). VC1 domain is responsible for binding to the majority of RAGE ligands including advanced glycation end products (AGEs), S100 proteins, and HMGB1. To ascertain whether other ligands exist, we analyzed by MS the material pulled down by VC1 from human plasma. Twenty of 295 identified proteins were selected and associated to coagulation and complement processes and to extracellular matrix. Four of them contained a γ-carboxyl glutamic acid (Gla) domain, a calcium-binding module, and prothrombin (PT) was the most abundant. Using MicroScale thermophoresis, we quantified the interaction of PT with VC1 and sRAGE in the absence or presence of calcium that acted as a competitor. PT devoid of the Gla domain (PT des-Gla) did not bind to sRAGE, providing further evidence that the Gla domain is critical for the interaction. Finally, the presence of VC1 delayed plasma clotting in a dose-dependent manner. We propose that RAGE is involved in modulating blood coagulation presumably in conditions of lung injury.

Role of soluble receptor for advanced glycation end products in postoperative fibrotic lung injury

2021 ◽  
Author(s):  
Satoshi Nakao ◽  
Kakuhiro Yamaguchi ◽  
Hiroshi Iwamoto ◽  
Atsushi Kagimoto ◽  
Takahiro Mimae ◽  
...  
Keyword(s):  
Lung Injury ◽  
Advanced Glycation End Products ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Anti-degenerative effect of Apigenin, Luteolin and Quercetin on human keratinocyte and chondrocyte cultures: SAR evaluation

Drug Research ◽  
2017 ◽  
Vol 68 (03) ◽  
pp. 132-138 ◽  
Author(s):  
Lucia Crascì ◽  
Venera Cardile ◽  
Giusy Longhitano ◽  
Francesco Nanfitò ◽  
Annamaria Panico
Keyword(s):  
Advanced Glycation End Products ◽  
Cell Injury ◽  
Protective Role ◽  
Hydroxyl Groups ◽  
Advanced Glycation ◽  
Pharmacological Activities ◽  
Tissue Degeneration ◽  
Glycation End Products ◽  
End Products ◽  
Biological Substrate

Abstract Background Inflammation is a dynamic process that occur on vascularized tissue in response to different stimuli causing cell injury and tissue degeneration. Reactive oxygen and nitrogen species (ROS and RNS) and advanced glycation end products (AGEs) have a key mediatory role in the development and progression of degenerative tissue process. The bioflavonoids possess a broad-spectrum of pharmacological activities. Their capability is related to their chemical structure. Methods In this study we evaluated and compare antioxidant, anti-glycative and anti-degenerative actions of two flavones apigenin and luteolin and a flavonol quercetin, in function of their hydroxyl groups arrangement. Moreover we assay, on NCTC 2544 and chondrocytes cultures, the flavonoids capacity to modulate NO and glycosamminoglycans levels, index of antidegenerative capacity. Results All tested flavonoids act as free radicals scavengers (ROO• and NO•) and advanced glycation end products inhibitors, in agreement with their BDE, IP and molecular planarity. Quercetin showed a high ORAC value (2.70±0.12 ORAC Units), according to a low BDE (74.54 Kcal/mol) and IP (174.44 Kcal/mol) values. Luteolin is the most active compound in the NO (48.19±0.18%) and AGEs (60.06±0.52%) inhibition, in function of a low torsion angle (16.3°) between the 3-OH moiety and C’6 carbon atom. Conclusion All tested flavonoids posses a protective role on degenerative tissue events. They acts in different manner depending on the functional groups, the biological substrate and the concentration used. In any case, it can be considered a suitable product preventing a degenerative processes.

scholarly journals Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury

Thorax ◽  
2008 ◽  
Vol 63 (12) ◽  
pp. 1083-1089 ◽  
Author(s):  
C S Calfee ◽  
L B Ware ◽  
M D Eisner ◽  
P E Parsons ◽  
B T Thompson ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Clinical Outcomes ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Receptors for Advanced Glycation End-Products Targeting Protect against Hyperoxia-Induced Lung Injury in Mice

2010 ◽  
Vol 42 (5) ◽  
pp. 545-551 ◽  
Author(s):  
Paul R. Reynolds ◽  
Robert E. Schmitt ◽  
Stephen D. Kasteler ◽  
Anne Sturrock ◽  
Karl Sanders ◽  
...  
Keyword(s):  
Lung Injury ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products
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