The Receptor For Advanced Glycation End-Products (RAGE) Interacts With Focal Adhesion Molecules In Epithelial-Mesenchymal Transition (EMT) Of Alveolar Epithelial Cells

2011 ◽  
Author(s):  
Carsten Ehrhardt ◽  
Carlos Medina ◽  
Stephen T. Buckley
Keyword(s):  
Epithelial Cells ◽  
Focal Adhesion ◽  
Advanced Glycation End Products ◽  
Epithelial Mesenchymal Transition ◽  
Alveolar Epithelial Cells ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
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.

scholarly journals 3H-1,2-Dithiole-3-Thione Protects Lens Epithelial Cells against Fructose-Induced Epithelial-Mesenchymal Transition via Activation of AMPK to Eliminate AKR1B1-Induced Oxidative Stress in Diabetes Mellitus

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1086
Author(s):  
Tsung-Tien Wu ◽  
Ying-Ying Chen ◽  
Chiu-Yi Ho ◽  
Tung-Chen Yeh ◽  
Gwo-Ching Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Epithelial Mesenchymal Transition ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products

Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs were isolated during cataract surgery from patients without DM or with DM. In a rat model, fructose (10% fructose, eight weeks) with or without D3T (10 mg/kg/day) treatment induced DM, as verified by blood pressure and serum parameter measurements. We observed that the formation of advanced glycation end products (AGEs) was significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Aldose reductase (AKR1B1), AcSOD2, and 3-NT were significantly enhanced in the rat lens epithelial sections of fructose-induced DM, however, the phosphorylation level of AMPKT172 showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPKT172 may be required for reduced superoxide generation and the pathogenesis of diabetic cataract. Administration of D3T reverses the fructose-induced EMT formation the LECs of fructose-induced DM. These novel findings suggest that the D3T may be a candidate for the pharmacological prevention of cataracts in patients with DM.

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.

HMGB1 Enhances the AGE-Induced Expression of CTGF and TGF-β via RAGE-Dependent Signaling in Renal Tubular Epithelial Cells

2015 ◽  
Vol 41 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Meichu Cheng ◽  
Hong Liu ◽  
Dongshan Zhang ◽  
Yinghong Liu ◽  
Chang Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Tubular Epithelial Cells ◽  
Advanced Glycation ◽  
Induced Expression ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products ◽  
Renal Tubular

Background/Aims: Advanced glycation end products (AGEs) induce epithelial mesenchymal transition (EMT) in renal proximal tubular epithelial cells (PTECs) by promoting the two EMT regulators, transforming growth factor beta (TGF-β) and connective tissue growth factor (CTGF). However, the exact signaling mechanism remains largely unclear. Methods: We investigated the promotion to high mobility group box 1 (HMGB1) in renal tubular epithelial HK-2 cells by AGE-BSA with quantitative PCR and western blot assay, and then determined the regulatory role of HMGB1 in the AGE-BSA-induced CTGF and TGF-β. In addition, the dependence of the receptor of advanced glycation end products (RAGE) was also examined in the CTGF and TGF-β promotion by AGEs and HMGB1 in HK-2 cells using the RNAi method. Results: It was demonstrated that AGEs induced translocation and release of HMGB1 from tubular epithelial HK-2 cells, and the released HMGB1 enhanced the promotion to CTGF and TGF-β by AGEs in HK-2 cells. On the other side, the HMGB1 knockdown by siRNA attenuated the AGE-BSA-induced expression of TGF-β. Moreover, the CTGF and TGF-β promotion in HK-2 cells by AGEs and HMGB1 was RAGE-dependent. Conclusion: Our results indicated that AGEs induced HMGB-1 and promoted the CTGF and TGF-β in renal epithelial HK-2 cells RAGE-dependently. And there was a synergism between AGEs and HMGB1 in the RAGE signaling activation. The in vitro data suggested that the AGE-RAGE and HMGB-1-RAGE signaling might play an important role in the promotion of CTGF and TGF-β in the renal fibrosis process of diabetic nephropathy.

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.

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