miR-3934 suppresses basophil apoptosis and secretion of inflammatory cytokines by targeting RAGE in asthma

2021 ◽  
Author(s):  
Kaiyu Han ◽  
Liyan Dou ◽  
Junwei Wang ◽  
Wenyu Wang ◽  
Hong Chen ◽  
...  
Keyword(s):  
Western Blot ◽  
Inflammatory Cytokines ◽  
Advanced Glycation End Products ◽  
Expression Level ◽  
Operating Characteristics ◽  
Advanced Glycation ◽  
Smad Signaling ◽  
Asthmatic Patients ◽  
Glycation End Products ◽  
End Products

Abstract Background Several miRNAs are now known to have clear connections to the pathogenesis of asthma. The present study focused on the potential role of miR-3934 during asthma development. Methods The basophils was isolated from 50 asthmatic patients and 50 health controls. The expression level of miR-3934 was examined by RT-qPCR and the expression of receptor for advanced glycation end products (RAGE) was detected by western blot. In addition, the analysis of apoptotic basophils was performed by flow cytometry; the expression level of inflammatory cytokines was detected by ELISA kits; and several important proteins in TGF-β/Smad signaling were examined by western blot. Results miR-3934 was down-regulated in the basophils of asthmatic patients. The expression of the pro-inflammatory cytokines IL-6, IL-8 and IL-33 was enhanced in basophils from asthmatic patients, and this effect was partially reversed by transfection of miR-3934 mimics. Furthermore, receiver operating characteristics analysis showed that miR-3934 levels can be used to distinguish asthma patients from healthy individuals. miR-3934 partially inhibited advanced glycation end products-induced increases in basophil apoptosis by suppressing expression of RAGE. Conclusion Our results indicate that miR-3934 acts to mitigate the pathogenesis of asthma by targeting RAGE and suppressing TGF-β/Smad signaling.

scholarly journals Dysregulation of Receptor for Advanced Glycation End Products (RAGE) Expression as a Biomarker of Keratoconus

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Valentin Navel ◽  
Jean Malecaze ◽  
Corinne Belville ◽  
Héléna Choltus ◽  
Fanny Henrioux ◽  
...  
Keyword(s):  
Western Blot ◽  
Advanced Glycation End Products ◽  
Corneal Epithelium ◽  
Controlled Study ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
First Time ◽  
Rage Expression ◽  
Corneal Collagen

Background. Because of the implications of Receptor for Advanced Glycation End Products (RAGE) in keratoconus (KC), we describe a differential expression of RAGE transcripts and proteins in corneal tissues and tears of KC and healthy patients. Methods. Using a case-controlled study, corneal epitheliums and tears of KC and healthy subjects were obtained during corneal collagen cross-linking and photorefractive keratectomy (PKR) and during usual consultations. Quantitative reverse transcription (RT-qPCR) and Western-Blot were performed to analyze RAGE transcripts and proteins’ expression in corneal tissues and tears. Results. One hundred and six patients were included in this study. The characteristics of the patients were as follows: 56 KC (25 corneal epithelium and 31 tears) and 50 control subjects (25 corneal epithelium and 25 tears). Transcripts of RAGE, HMGB1, and S100 family ligands were quantified by RT-qPCR, identifying a significantly higher expression of RAGE and HMGB1 in the healthy group than in the KC group ( p = 0.03 and 0.04, respectively). Western Blot showed a significantly higher fl-RAGE expression in KC corneal epithelium than control ( p < 0.001 ) and lower s-RAGE expression in KC tears than control ( p = 0.04 ). Conclusions. Linked with the inflammatory process occurring in KC pathophysiology, we propose for the first time that the RAGE expression (total and truncated forms of receptor and ligands) in KC corneal tissues and tear samples provides viable biomarkers.

scholarly journals Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Biomarker of COPD 

2020 ◽  
Author(s):  
Katherine A. Pratte ◽  
Jeffery L. Curtis ◽  
Katerina Kechris ◽  
David Couper ◽  
Michael H. Cho ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Meta Analysis ◽  
Airflow Obstruction ◽  
Minor Allele ◽  
Soluble Receptor ◽  
Operating Characteristics ◽  
Advanced Glycation ◽  
Lung Density ◽  
Glycation End Products ◽  
End Products

Abstract Background:Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publication have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes.Methods: sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n=1,443), SPIROMICS (n=1,623); ECLIPSE (n=2,349); Pittsburgh COPD SCCOR (n=399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity).Results: Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P<0.001), reduced FEV1 (P < 0.001), and emphysema severity (P<0.001). In an inverse-variance weighted meta-analysis, one SD lower log10-transformed sRAGE was associated with 105 ± 22 mL lower FEV1 and 4.14 ± 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV1 decline and emphysema progression only in the ECLIPSE cohort. Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar. Conclusions: Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed. In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling. Thus, genotype should be included in sRAGE evaluations.

scholarly journals FOXO1 Mediates Advanced Glycation End Products Induced Mouse Osteocyte-Like MLO-Y4 Cell Apoptosis and Dysfunctions

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Citong Zhang ◽  
Wei Wei ◽  
Minghan Chi ◽  
Yao Wan ◽  
Xue Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Advanced Glycation End Products ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Bone Homeostasis ◽  
Advanced Glycation ◽  
Osteocyte Apoptosis ◽  
Glycation End Products ◽  
End Products

Osteocyte plays an essential role in bone metabolism by regulating osteoblast and osteoclast activities. Dysfunction or apoptosis of osteocyte will severely endanger the bone homeostasis and result in bone diseases such as osteoporosis. Osteoporosis has been considered as one of the diabetes complications; however, the mechanism is still to be discovered. Advanced glycation end products (AGEs), as the main pathogenic factor of diabetes mellitus, have the capacity to induce osteocyte apoptosis thus sabotaging bone homeostasis. Here, we examined the role of AGE during osteocyte apoptosis and how this effect would affect osteocyte’s regulation of osteoblast and osteoclast. Mouse osteocyte-like MLO-Y4 cells were used to study the properties of osteocyte and to examine its biological and pathological function. MTT assay and Annexin V assay showed that AGE significantly induce MLO-Y4 cell apoptosis. qPCR and Western blot results have shown that AGE upregulates proapoptotic gene p53 and its downstream target gene Bax, which leads to enhanced activation of caspase-3, thus inducing apoptosis in MLO-Y4 cells. Increased expression of sclerostin and RANKL in osteocytes has shown that AGE induces osteocyte dysfunction thus severely damaging the bone homeostasis by decreasing osteoblast and increasing osteoclast activities. Furthermore, the role of the transcription factor FOXO1, which is intensely associated with apoptosis, has been determined. Western blot has shown that AGE significantly decreases Akt activities. Immunofluorescence has shown that AGE promotes FOXO1 nuclei localization and enhances FOXO1 expression. Silencing of FOXO1 suppressed AGE-enhanced apoptosis; mRNA and protein expressions of cleaved caspase-3, sclerostin, and RANKL were downregulated as well. Moreover, exogenous FOXO1 increased caspase-3 mRNA levels and caspase-3 transcriptional activity. Lastly, ChIP assay has established the capacity of FOXO1 binding directly on the caspase-3, sclerostin, and RANKL promoter region in AGE environment, providing the mechanism of the AGE-induced osteocyte apoptosis and dysfunction. Our results have shown that FOXO1 plays a crucial role in AGE-induced osteocyte dysfunction and apoptosis through its regulation of caspase-3, sclerostin, and RANKL. This study provides new insight into diabetes-enhanced risk of osteoporosis given the critical role of AGE in the pathogenesis of diabetes and the essential part of osteocyte in bone metabolism.

Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats

2016 ◽  
Vol 94 (3) ◽  
pp. 332-340 ◽  
Author(s):  
Jun Hou ◽  
Dezhi Zheng ◽  
Gabriel Fung ◽  
Haoyu Deng ◽  
Lin Chen ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Diabetic Cardiomyopathy ◽  
Advanced Glycation End Products ◽  
High Fat Diet ◽  
Nuclear Translocation ◽  
High Fat ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Mrna And Protein Expression

Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1β). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM.

miR-3934 suppresses basophil apoptosis and secretion of inflammatory cytokines by targeting RAGE in asthma

2021 ◽  
Author(s):  
Kaiyu Han ◽  
Liyan Dou ◽  
Junwei Wang ◽  
Wenyu Wang ◽  
Hong Chen ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Potential Role ◽  
Operating Characteristics ◽  
Advanced Glycation ◽  
Asthmatic Patients ◽  
Glycation End Products ◽  
Asthma Patients ◽  
Characteristics Analysis ◽  
Pro Inflammatory Cytokines

Abstract Background Several miRNAs are now known to have clear connections to the pathogenesis of asthma. The present study focused on the potential role of miR-3934 during asthma development. Results miR-3934 was down-regulated in the basophils of asthmatic patients. The expression of the pro-inflammatory cytokines IL-6, IL-8 and IL-33 was enhanced in basophils from asthmatic patients, and this effect was partially reversed by transfection of miR-3934 mimics. Furthermore, receiver operating characteristics analysis showed that miR-3934 levels can be used to distinguish asthma patients from healthy individuals. miR-3934 partially inhibited advanced glycation end products-induced increases in basophil apoptosis by suppressing expression of RAGE. Conclusion Our results indicate that miR-3934 acts to mitigate the pathogenesis of asthma by targeting RAGE and suppressing TGF-β/Smad signaling.

scholarly journals Advanced glycation end-products activate the renin-angiotensin system through the RAGE/PI3-K signaling pathway in podocytes

2012 ◽  
Vol 35 (5) ◽  
pp. 282 ◽  
Author(s):  
Cailan L. Cheng ◽  
Ying Tang ◽  
Zhenda Zheng ◽  
Xun Liu ◽  
Zengchun C. Ye ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Western Blot ◽  
Advanced Glycation End Products ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Advanced Glycation ◽  
Angiotensin System ◽  
Glycation End Products ◽  
End Products ◽  
Ace Activity

Purpose: The purpose of this study was to investigate the effects of advanced glycation end-products (AGEs) on the components of the renin-angiotensin system (RAS) in podocytes and to understand the mechanism of these effects. Methods: Immortalized mouse podocytes were exposed to various concentrations of AGEs for different time intervals. The expression levels of angiotensinogen (AGT), angiotensin II type 1 and 2 receptors (AT1R and AT2R) and renin were examined by real-time PCR and western blot; the receptor for AGEs (RAGE) and both Akt and phosphorylated Akt were examined by western blot; levels of angiotensin II (Ang II) were assayed by ELISA, and the activity of angiotensin-converting enzyme (ACE) was evaluated by measuring the production of hippuric acid in vitro. Results: Treatment with AGEs resulted in significant increases in the expression of AGT (62%, P=0.002) and AT1R (59%, P=0.01). Moreover, Ang II levels increased significantly in both cell lysates (70%, P=0.018) and conditioned media (65%, P=0.01). ACE activity was also significantly higher in cell lysates (68% , P= 0.035) and conditioned media (65%, P=0.023). There were no changes in renin or AT2R expression (P > 0.05). AGEs did increase the expression of RAGE by 50% (P=0.012) and the phosphorylation of Akt by 100% (P=0.001). When podocytes were pretreated with anti-RAGE antibody (50 µg/ml) or the phosphoinositide 3-kinase (PI3-K) inhibitor, LY294002 (10 µM), the AGEs-induced increases in AGT and AT1R expression were reduced. Likewise, Ang II levels and ACE activity decreased significantly. Conclusion: AGEs activate the RAS in podocytes through the RAGE-PI3-K/Akt-dependent pathway and lead to an increase in podocyte apoptosis.

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