The receptor for advanced glycation end-products enhances lung epithelial wound repair: An in vitro study

Zhai, Ruoyang; Blondonnet, Raïko; Ebrahimi, Ebrahim; Belville, Corinne; Audard, Jules; Gross, Christelle; Choltus, Héléna; Henrioux, Fanny; Constantin, Jean-Michel; Pereira, Bruno; Blanchon, Loı̈c; Sapin, Vincent; Jabaudon, Matthieu

doi:10.1016/j.yexcr.2020.112030

Cited by 8 publications

(4 citation statements)

References 55 publications

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“…These cells most express RAGE in the lung, which is strongly associated with IPF pathogenesis [24]. RAGE pathway has been reported lung alveolar epithelial wound healing through cell migration and proliferation enhancement in vitro [25]. The RAGE is expressed and distinctly regulated in respiratory diseases.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Upregulation of sRAGE may impair the amphoterin-and RAGE-mediated stimulation of cancer growth and migration [22]. Studies on human alveolar epithelial A549 cells have suggested that the RAGE axis is involved in the repair of lung epithelial cells and perhaps also in cell migration and proliferation [23]. However, sRAGE level decreases in lung cancer patients [10,12,17] but increases in those with other types of cancer [7,8].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Utility and Tendency of Bronchial and Serum Soluble Receptor for Advanced Glycation EndProducts (sRAGE) in Lung Cancer

Kim

Choi

et al. 2023

Cancers

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The receptor for advanced glycation end-products (RAGE) may serve as a diagnostic and prognostic biomarker of lung cancer and lung injury. We explored whether the serum and bronchial levels of soluble RAGE (sRAGE) distinguished infectious lung diseases from lung cancer. We collected serum and bronchial washing fluids (BWFs) from patients diagnosed with pneumonia, tuberculosis, or preoperative lung cancer from April 2016 to March 2022. sRAGE levels were measured using an enzyme-linked immunosorbent assay and we drew receiver operating characteristic (1) curves to determine the cut-off values affording the best diagnostic sensitivities. We enrolled 81 patients including 20 with tuberculosis, 30 with pneumonia, and 31 with lung cancer. Of the 81, 61% were males and the median age was 66 years. The median serum level of sRAGE was 822 (678–1168 pg/mL) and did not differ significantly between the three groups. The median bronchial sRAGE level was 167 (83–529 pg/mL) but 231 (108–649 pg/mL) for tuberculosis, 366 (106–706 pg/mL) for pneumonia, and 103 (32–254 pg/mL) for lung cancer patients (p = 0.018). The ROC curve for the bronchial sRAGE values of lung cancer patients revealed that the optimal cut-off was 118.9 pg/mL. This afforded a sensitivity of 76%, a specificity of 58%, and an area under the ROC curve of 0.695 (p = 0.005). The level of bronchial sRAGE differed significantly between patients with lung cancer and other respiratory diseases; that level may serve as an auxiliary diagnostic biomarker.

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“… 32 In vitro , genetic inhibition of RAGE had no effects on bleomycin or asbestos-induced cell death, but reduced epithelial cell adhesion, increased proliferation, migration, and wound-healing capacity. 32 , 60 In addition, Zhai et al 63 recently demonstrated that stimulation of alveolar epithelial cells with AGEs and HMGB1 promoted wound-healing capacity and proliferation in a RAGE-dependent manner. In line with this, previous studies demonstrated that RAGE on AEC1 cells binds to collagen and facilitates cell adhesion/spreading.…”

Section: The Puzzling Role Of Rage In Experimental Models Of Ipfmentioning

confidence: 99%

The perplexing role of RAGE in pulmonary fibrosis: causality or casualty?

Perkins

Oury

2021

Ther Adv Respir Dis

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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease in which most patients die within 3 years of diagnosis. With an unknown etiology, IPF results in progressive fibrosis of the lung parenchyma, diminishing normal lung function, which results in respiratory failure, and eventually, death. While few therapies are available to reduce disease progression, patients continue to advance toward respiratory failure, leaving lung transplantation the only viable option for survival. As incidence and mortality rates steadily increase, the need for novel therapeutics is imperative. The receptor for advanced glycation endproducts (RAGE) is most highly expressed in the lungs and plays a significant role in a number of chronic lung diseases. RAGE has long been linked to IPF; however, confounding data from both human and experimental studies have left an incomplete and perplexing story. This review examines the present understanding of the role of RAGE in human and experimental models of IPF, drawing parallels to recent advances in RAGE biology. Moreover, this review discusses the role of RAGE in lung injury response, type 2 immunity, and cellular senescence, and how such mechanisms may relate to RAGE as both a biomarker of disease progression and potential therapeutic target in IPF. The reviews of this paper are available via the supplemental material section.

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The receptor for advanced glycation end-products enhances lung epithelial wound repair: An in vitro study

Cited by 8 publications

References 55 publications

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

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

Diagnostic Utility and Tendency of Bronchial and Serum Soluble Receptor for Advanced Glycation EndProducts (sRAGE) in Lung Cancer

The perplexing role of RAGE in pulmonary fibrosis: causality or casualty?

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