Type II Alveolar Epithelial Cells in Lung Express Receptor for Advanced Glycation End Products (RAGE) Gene

1997 ◽  
Vol 238 (2) ◽  
pp. 512-516 ◽  
Author(s):  
Fumiki Katsuoka ◽  
Yasushi Kawakami ◽  
Takeo Arai ◽  
Hiroyuki Imuta ◽  
Masachika Fujiwara ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Advanced Glycation ◽  
Alveolar Epithelial ◽  
Glycation End Products ◽  
End Products

scholarly journals Proteolytic release of the receptor for advanced glycation end products from in vitro and in situ alveolar epithelial cells

2011 ◽  
Vol 300 (4) ◽  
pp. L516-L525 ◽  
Author(s):  
Naoko Yamakawa ◽  
Tokujiro Uchida ◽  
Michael A. Matthay ◽  
Koshi Makita
Keyword(s):  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Alveolar Epithelial Cells ◽  
Advanced Glycation ◽  
Alveolar Epithelial ◽  
Lps Challenge ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Although the receptor for advanced glycation end products (RAGE) has been used as a biological marker of alveolar epithelial cell injury in clinical studies, the mechanism for release of soluble RAGE from lung epithelial cells has not been well studied. Therefore, these studies were designed to determine the mechanism for release of soluble RAGE after lipopolysaccharide (LPS) challenge. For these purposes, alveolar epithelial cells from rat lungs were cultured on Transwell inserts, and LPS was added to the apical side (500 μg/ml) for 16 h on day 7. On day 7, RAGE was expressed predominantly in surfactant protein D-negative cells, and LPS challenge induced release of RAGE into the medium. This response was partially blocked by matrix metalloproteinase (MMP) inhibitors. Transcripts of MMP-3 and MMP-13 were upregulated by LPS, whereas RAGE transcripts did not change. Proteolysis by MMP-3 and MMP-13 resulted in soluble RAGE expression in the bronchoalveolar lavage fluid in the in situ rat lung, and this reaction was inhibited by MMP inhibitors. In human studies, both MMP-3 and -13 antigen levels were significantly correlated with the level of RAGE in pulmonary edema fluid samples. These results support the conclusion that release of RAGE is primarily mediated by proteolytic damage in alveolar epithelial cells in the lung, caused by proteases in acute inflammatory conditions in the distal air spaces.

The Potential of Receptor for Advanced Glycation End Products (RAGE) as a Therapeutic Target for Lung Associated Diseases

2019 ◽  
Vol 20 (6) ◽  
pp. 679-689 ◽  
Author(s):  
Tejinder Pal Khaket ◽  
Sun Chul Kang ◽  
Tapan Kumar Mukherjee
Keyword(s):  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Chronic Obstructive ◽  
Advanced Glycation ◽  
Comprehensive Overview ◽  
Associated Diseases ◽  
Glycation End Products ◽  
End Products

The receptor for advanced glycation end products (RAGE) is a multi-ligand pattern recognition receptor that is highly expressed in lung epithelial cells. It helps alveolar epithelial cells to maintain their morphology and specific architecture. However, in various pathophysiological conditions, pulmonary tissues express a supraphysiological level of RAGE and its ligands including advanced glycation end products, high mobility group box 1 proteins, and S100 proteins. On interaction with RAGE, these ligands stimulate downstream signaling that generates inflammation and oxidative stress leading to asthma, chronic obstructive pulmonary disease, lung cancers, idiopathic pulmonary fibrosis, acute lung injury, pneumonia, bronchopulmonary dysplasia, cystic fibrosis, and sepsis. Thus, pharmacological agents that can either suppress the production of RAGE or block its biological activity would offer promising therapeutic value against pathogenesis of the aforementioned lungassociated diseases. This review presents a comprehensive overview of the recent progress made in defining the functions of RAGE in lung-associated diseases.

The role of the receptor for advanced glycation end-products in lung fibrosis

2007 ◽  
Vol 293 (6) ◽  
pp. L1427-L1436 ◽  
Author(s):  
Mei He ◽  
Hiroshi Kubo ◽  
Kota Ishizawa ◽  
Ahmed E. Hegab ◽  
Yasuhiko Yamamoto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Advanced Glycation End Products ◽  
Lung Fibrosis ◽  
Alveolar Type ◽  
Type Ii ◽  
Wild Type ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

The pathogenesis of pulmonary fibrosis remains unclear. The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor known to be involved in the process of fibrotic change in several organs, such as peritoneal fibrosis and kidney fibrosis. The aim of this study was to examine the contribution of RAGE during the acute inflammation and chronic fibrotic phases of lung injury induced by intratracheal instillation of bleomycin in mice. Bleomycin-induced lung fibrosis was evaluated in wild-type and RAGE-deficient (RAGE−/−) mice. Bleomycin administration to wild-type mice caused an initial pneumonitis that evolved into fibrosis. While RAGE−/− mice developed a similar early inflammatory response, the mice were largely protected from the late fibrotic effects of bleomycin. The protection afforded by RAGE deficiency was accompanied by reduced pulmonary levels of the potent RAGE-inducible profibrotic cytokines transforming growth factor (TGF)-β and PDGF. In addition, bleomycin administration induced high mobility group box 1 (HMGB-1) production, one of the ligands of RAGE, from inflammatory cells that accumulated within the air space. Coculture with HMGB-1 induced epithelial-mesenchymal transition (EMT) in alveolar type II epithelial cells from wild-type mice. However, alveolar type II epithelial cells derived from RAGE−/− mice did not respond to HMGB-1 treatment, such that the RAGE/HMGB-1 axis may play an important role in EMT. Also, bleomycin administration induced profibrotic cytokines TGF-β and PDGF only in wild-type mouse lungs. Our results suggested that RAGE contributes to bleomycin-induced lung fibrosis through EMT and profibrotic cytokine production. Thus, RAGE may be a new therapeutic target for pulmonary fibrosis.

scholarly journals Reduced receptor for advanced glycation end products is associated with α-SMA expression in patients with idiopathic pulmonary fibrosis and mice

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Hyosin Baek ◽  
Soojin Jang ◽  
Jaehyun Park ◽  
Jimin Jang ◽  
Jooyeon Lee ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Western Blot ◽  
Advanced Glycation End Products ◽  
Alveolar Epithelial Cells ◽  
Advanced Glycation ◽  
Alveolar Epithelial ◽  
Glycation End Products ◽  
End Products ◽  
Rage Expression

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Despite alveolar epithelial cells is crucial role in lung, its contribution and the associated biomarker remain unknown in the pathogenesis of IPF. Recently, environmental factors including stone dust, silica and cigarette smoking were found as risk factors involved in IPF. Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin super family of cell surface receptors. It has been shown that interaction between RAGE and its ligands on immune cells mediates cellular migration and regulation of pro-inflammation. RAGE is highly expressed in the lung, in particular, alveolar epithelial cells. Therefore, we determined whether RAGE expression is associated with fibrosis-associated genes in patients with IPF and mice. Results When bleomycin (BLM) was intratracheally administered to C57BL/6 mice for 1, 2 weeks, macrophage and neutrophils were significantly increased. The fibrotic nodule formed and accumulation of collagen was determined after BLM injection in H&E- and Masson’s trichrome staining. Levels of elastin, Col1a1 and fibronectin were increased in quantitative real-time PCR and protein levels of α-SMA was increased in western blot analysis. In the lung tissues of 1 mg/kg BLM-induced mice, RAGE expression was gradually decreased in 1- and 2 weeks in immunohistochemistry and western blot analysis, and 3 mg/kg of BLM-induced mice exhibited decreased RAGE levels while α-SMA expression was increased. We next determined RAGE expression in the lungs of IPF patients using immunohistochemistry. As a result, RAGE expression was decreased, while α-SMA expression was increased compared with non-IPF subjects. Conclusions Our findings suggest that reduced RAGE was associated with increased fibrotic genes in BLM-induced mice and patients with IPF. Therefore, RAGE could be applied with a biomarker for prognosis and diagnosis in the pathogenesis of IPF.

Advanced glycation end-products associate with podocytopathy in type II diabetic patients

2021 ◽  
Author(s):  
Rajkishor Nishad ◽  
Tahaseen V Syed ◽  
Manga Motrapu ◽  
Rajesh Kavvuri ◽  
Kiranmayi Kodali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Advanced Glycation End Products ◽  
Diabetic Patients ◽  
Type Ii ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine

Abstract Background The prevalence of diabetes reaches epidemic proportions, affecting the incidence of diabetic nephropathy (DN) and associated end-stage kidney disease (ESKD). Diabetes is the leading cause of ESKD since 30–40% of diabetic patients develop DN. Albuminuria and eGFR have been considered a surrogate outcome of chronic kidney disease, and the search for a biomarker that predicts progression to diabetic kidney disease is intense.Methods We analyzed the association of serum advanced glycation end-products (AGEs) index (AGI) with impaired kidney function in uncontrolled diabetic patients (type II, n = 130) with albuminuria ranging from (150 to 450 mg/day). The kidney biopsy specimens were also examined for the association of AGEs, particularly carboxymethyl lysine (CML) with kidney function. Further, we also assessed the effect of carboxymethyl lysine on glomerular injury and podocytopathy in experimental animals.Results We observed a strong correlation between AGI and impaired kidney function in miroalbuminuric patients with hyperglycemia. A significant association between CML levels and impaired kidney function was noticed. Administration of CML in mice showed heavy proteinuria and glomerular abnormalities. Reduced podocyte number observed in mice administered with CML could be attributed to the epithelial-mesenchymal transition (EMT) of podocytes. Conclusion Serum AGEs could be independently related to the podocyte injury vis-a-vis the risk of DN progression to ESKD in patients with microalbuminuria. AGEs or CML could be considered a prognostic marker to assess microalbuminuria progression to ESKD in diabetic patients.

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