scholarly journals Potential of an Interorgan Network Mediated by Toxic Advanced Glycation End-Products in a Rat Model

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 80
Author(s):  
Shinya Inoue ◽  
Takanobu Takata ◽  
Yusuke Nakazawa ◽  
Yuka Nakamura ◽  
Xin Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Advanced Glycation End Products ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Advanced Glycation ◽  
High Fructose ◽  
Glycation End Products ◽  
End Products ◽  
Liver And Kidney

Excessive intake of glucose and fructose in beverages and foods containing high-fructose corn syrup (HFCS) plays a significant role in the progression of lifestyle-related diseases (LSRD). Glyceraldehyde-derived advanced glycation end-products (AGEs), which have been designated as toxic AGEs (TAGE), are involved in LSRD progression. Understanding of the mechanisms underlying the effects of TAGE on gene expression in the kidneys remains limited. In this study, DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were used to investigate whether HFCS-consuming Wister rats generated increased intracellular serum TAGE levels, as well as the potential role of TAGE in liver and kidney dysfunction. HFCS consumption resulted in significant accumulation of TAGE in the serum and liver of rats, and induced changes in gene expression in the kidneys without TAGE accumulation or upregulation of receptor for AGEs (RAGE) upregulation. Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines without IL-1β and TNF-α is suggested to contribute to the observed changes in kidney gene expression.

Abstract 48: Role of Receptor for Advanced Glycation End Products (RAGE) in Regression of Diabetic Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Laura M Senatus ◽  
Raquel Lopez-Diez ◽  
Jianhua Liu ◽  
Huilin Li ◽  
Gurdip Daffu ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Expression Profiles ◽  
Advanced Glycation Endproducts ◽  
Gene Expression Profiles ◽  
Inflammatory Disorder ◽  
Advanced Glycation ◽  
Chronic Inflammatory Disorder ◽  
Glycation End Products ◽  
End Products

Atherosclerosis is a chronic inflammatory disorder. Both progression and regression of atherosclerosis are adversely affected by diabetes. A key player in these processes is Receptor for Advanced Glycation End Products (RAGE). RAGE is a multiligand cell surface macromolecule, which binds ligands enriched in atherosclerotic plaques, such as advanced glycation endproducts (AGEs). RAGE is expressed on a wide array of cell types implicated in cardiovascular disease, such as endothelial cells, and inflammatory cells such as macrophages. The cytoplasmic domain of RAGE binds to the formin molecule DIAPH1 and DIAPH1 is required for RAGE ligands to activate cell signaling responses. RAGE acts as a key mediator of oxidative and inflammatory signaling pathways that are involved in atherosclerosis. We tested mechanisms of impaired regression of atherosclerosis in a murine model of aorta transplantation and found that deletion of Ager or Diaph1 in diabetic mice recipients of Ldlr null mice atherosclerotic aortas accelerates atherosclerosis regression and significantly reduces the lesional macrophage content when compared to diabetic wild-type recipient mice. The antiatherosclerotic effects in diabetic Ager null mice and diabetic Diaph1 null mice include reduced RAGE ligand AGEs in transplanted aortas, with reduced expression of a range of proatherogenic factors, including reactive oxygen species and inflammatory cytokines implicated in leukocyte recruitment and activation. We employed RNA sequencing to identify the key transcriptional events by which RAGE mediates its effects in donor or recipient macrophages in diabetic regressing plaques. Our results suggest that critical gene expression profiles, including those genes involved in inflammation, endothelial dysfunction, oxidative stress, monocyte/macrophage fate (recruitment, differentiation, proliferation), signal transduction and lipid metabolism, are beneficially modulated, at least in part, via Ager deletion in atherosclerosis regression. Taken together, these data increase our understanding of the role of RAGE in diabetic atherosclerosis, particularly in macrophages, and may provide avenues for therapeutic strategies to accelerate regression of atherosclerosis in diabetes.

scholarly journals MiR-92b-3p is Induced by Advanced Glycation End Products and Involved in the Pathogenesis of Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Li-ping Wang ◽  
Jia-nan Geng ◽  
Bo Sun ◽  
Cheng-bo Sun ◽  
Yan Shi ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Rat Kidney ◽  
Luciferase Reporter ◽  
Control Group ◽  
Age Group ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Purpose. The current study aims to examine the effects of advanced glycation end products (AGEs) on the microRNA (miRNA) expression profile in the kidney tissues of rats. Methods. Wistar rats were randomly divided into three equal experiment groups: the AGE group, the RSA group, and the control group. The rats in the AGE group and the RSA group were administered with advanced glycation end products (AGEs) and rat serum albumin (RSA) via the tail vein, respectively, whereas the control group received PBS. Total RNA was prepared from the rat kidney tissues, and the miRNA expression profiles in different experiment groups were compared by microarray analysis. The expression levels of selected differential miRNAs were verified by RT-qPCR. Target gene prediction was conducted using algorithms such as TargetScan, miRanda, and PICTar. Functional analysis was performed to determine the putative biological roles of the validated miRNAs. Results. The microarray study revealed 451 upregulated and 320 downregulated miRNAs in the AGE group compared with the RSA group (p<0.05). Seven miRNAs, including miR-21-5p, miR-92b-3p, miR-140-3p, miR-196a-5p, miR-181b-5p, miR-186-5p, and miR-192-5p, were screened and verified using RT-qPCR, of which, the change of miR-92b-3p was the most obvious according to the miRNA expression different multiple and p value. Furthermore, the expression trend of miR-92b-3p measured by RT-qPCR was shown to be consistent with the microarray results. Bioinformatics analysis and luciferase reporter assay identified Smad7 was a direct target of miR-92b-3p. Both immunohistochemical and western blotting showed that Smad7 expression was significantly suppressed in the kidney tissues from the AGE group compared with the control and RSA groups. Conclusion. The results of the current study suggested that miR-92b-3p could mediate AGE-induced development of renal abnormalities through targeting Smad7 in rats with DN.

scholarly journals Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Taketoshi Noguchi ◽  
Toshiyuki Sado ◽  
Katsuhiko Naruse ◽  
Hiroshi Shigetomi ◽  
Akira Onogi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Advanced Glycation End Products ◽  
Expression Profiles ◽  
Receptor Activation ◽  
Advanced Glycation ◽  
Specific Expression ◽  
Downstream Signaling ◽  
Glycation End Products ◽  
End Products ◽  
Rage Expression

Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth.Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins.Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively.Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state.

scholarly journals Evidence for Toxic Advanced Glycation End-Products Generated in the Normal Rat Liver

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1612 ◽  
Author(s):  
Takanobu Takata ◽  
Akiko Sakasai-Sakai ◽  
Jun-ichi Takino ◽  
Masayoshi Takeuchi
Keyword(s):  
Rat Liver ◽  
Advanced Glycation End Products ◽  
Normal Liver ◽  
Advanced Glycation ◽  
Alcoholic Fatty Liver ◽  
Healthy Humans ◽  
High Fructose ◽  
Glycation End Products ◽  
End Products ◽  
Normal Rat

Glucose/fructose in beverages/foods containing high-fructose corn syrup (HFCS) are metabolized to glyceraldehyde (GA) in the liver. We previously reported that GA-derived advanced glycation end-products (toxic AGEs, TAGE) are generated and may induce the onset/progression of non-alcoholic fatty liver disease (NAFLD). We revealed that the generation of TAGE in the liver and serum TAGE levels were higher in NAFLD patients than in healthy humans. Although we propose the intracellular generation of TAGE in the normal liver, there is currently no evidence to support this, and the levels of TAGE produced have not yet been measured. In the present study, male Wister/ST rats that drank normal water or 10% HFCS 55 (HFCS beverage) were maintained for 13 weeks, and serum TAGE levels and intracellular TAGE levels in the liver were analyzed. Rats in the HFCS group drank 127.4 mL of the HFCS beverage each day. Serum TAGE levels and intracellular TAGE levels in the liver both increased in the HFCS group. A positive correlation was observed between intracellular TAGE levels in the liver and serum TAGE levels. On the other hand, in male Wister/ST rats that drank Lactobacillus beverage for 12 weeks—a commercial drink that contains glucose, fructose, and sucrose— no increases were observed in intracellular TAGE or serum TAGE levels. Intracellular TAGE were generated in the normal rat liver, and their production was promoted by HFCS, which may increase the risk of NAFLD.

scholarly journals Advanced Glycation End Products Inhibit Production and Activity of Matrix Metalloproteinase-2 in Human Umbilical Vein Endothelial Cells

2007 ◽  
Vol 35 (5) ◽  
pp. 709-715 ◽  
Author(s):  
L Gao ◽  
L Kang ◽  
Q Chen ◽  
C Chen ◽  
B Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Conditioned Medium ◽  
Advanced Glycation End Products ◽  
Umbilical Vein ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Umbilical Vein Endothelial Cells ◽  
Expression And Activity

The aim of this study was to investigate the effects of advanced glycation end products (AGEs) on the expression and activity of matrix metalloproteinases-2 (MMP-2) in human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were incubated with various concentrations of AGEs-modified albumin or unmodified albumin for different time periods. Protein and gene expression of MMP-2 and the receptor for AGEs (RAGE) were measured by Western blot and reverse transcription-polymerase chain reaction, respectively. The activity of MMP-2 in the conditioned medium was measured by gelatin zymography. The AGE-modified albumin inhibited MMP-2 but increased RAGE protein and gene expression in HUVECs in a concentration- and time-dependent manner. An inhibition of MMP-2 activity was also detected in the conditioned medium of HUVECs incubated with AGEs-modified albumin. In conclusion, AGEs inhibited the expression and activity of MMP-2 in HUVECs; this may be mediated through upregulation of RAGE.

Sign in / Sign up

Export Citation Format

Share Document