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

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.

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MiR-92b-3p is induced by advanced glycation end products and involved in the pathogenesis of diabetic nephropathy

10.7287/peerj.preprints.3026 ◽

2017 ◽

Author(s):

Wang Liping ◽

Geng Jia Nan ◽

Sun Bo ◽

Sun Chengbo ◽

Wang Siyuan ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Advanced Glycation End Products ◽

Mirna Expression ◽

Control Group ◽

Age Group ◽

Advanced Glycation ◽

Gene Target ◽

Qrt Pcr ◽

Glycation End Products ◽

End Products

Background. The current study aims to explore the effects of advanced glycation end products (AGEs) on the microRNA (miRNA) expression profile in kidney tissues in a murine diabetic nephropathy (DN) model, and to investigate the possible underlying mechanisms. Methods. Wister 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 AGEs and rat serum albumin (RSA) via the tail vein, respectively, whereas those in the control group received no injection. Following the extraction of total RNA from the murine kidney tissues, miRNA profiling was performed using a miRNA microarray to determine the global differences in miRNA expression between the three experiment groups. The identified panel of aberrantly expressed miRNA candidates were subsequently validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics analysis was performed to identify the target genes and enriched signaling pathway for the validated miRNAs. Results. Compared with RSA group, miR-7d-3p, miR-92b-3p, miR-181b-5p and miR-196c-5p were found to be significantly up-regulated in the AGE group, whereas miR-7a-1-3p, miR-186-5p, miR-192-5P, miR-196b-5p and miR-345-5p were shown to be down-regulated (p<0.05). Among the nine miRNA candidates, miR-92b-3p was validated by qRT-PCR analysis. Subsequent bioinformatic study indicated that SMAD7 could be a potential downstream gene target of miR-92b-3p. Both immunohistochemical staining and western blotting showed that SMAD7 expression was significantly suppressed in the kidney tissues harvested from the AGE group compared to those from the control and the RSA group. Discussion. The results of the current study revealed a correlation between increased renal level of miR-92b-3p and elevated serum level of AGEs in a murine model of DN.

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MiR-92b-3p is induced by advanced glycation end products and involved in the pathogenesis of diabetic nephropathy

10.7287/peerj.preprints.3026v1 ◽

2017 ◽

Cited By ~ 1

Author(s):

Wang Liping ◽

Geng Jia Nan ◽

Sun Bo ◽

Sun Chengbo ◽

Wang Siyuan ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Advanced Glycation End Products ◽

Mirna Expression ◽

Control Group ◽

Age Group ◽

Advanced Glycation ◽

Gene Target ◽

Qrt Pcr ◽

Glycation End Products ◽

End Products

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

Mediators of Inflammation ◽

10.1155/2010/490406 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 23

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.

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Calprotectin and Receptor for Advanced Glycation End Products as a Potential Biomarker in Abdominal Aortic Aneurysm

Journal of Clinical Medicine ◽

10.3390/jcm9040927 ◽

2020 ◽

Vol 9 (4) ◽

pp. 927

Author(s):

Willy Hauzer ◽

Wojciech Witkiewicz ◽

Jan Gnus

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Advanced Glycation End Products ◽

Endovascular Aneurysm Repair ◽

Control Group ◽

Advanced Glycation ◽

Abdominal Aortic ◽

Potential Biomarker ◽

Glycation End Products ◽

End Products

Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the diameter of the abdominal aorta was found. The purpose of this study was to investigate whether calprotectin and the RAGE plasma level may be a biomarker of human AAA occurrence. We determined two groups of research participants: a group of 32 patients aged 53–88 undergoing primary endovascular aneurysm repair and a control group of 43 volunteers aged 59–82 without the AAA. All the patients from the study group had their blood samples drawn in order to determine the level of calprotectin and RAGE in plasma. The second follow-up examination was carried out after three months. The concentration of calprotectin and RAGE in plasma was determined with the use of the immunoenzymatic method (ELISA). The study showed that patients with the AAA had significantly higher mean calprotectin and RAGE plasma levels (p = 0.0001 and p = 0.0002, respectively) as compared to the control group. After the AAA repair operations, the level of concentration of the calprotectin decreased significantly (p = 0.0002). So far, no studies on the connection between the increase of the calprotectin and RAGE in the patient’s plasma with the AAA have been published. Calprotectin may be a promising biomarker related to the occurrence of AAA. Larger studies are needed to fully elucidate and confirm the role of calprotectin in the development and progression of the aneurysm.

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Cardioprotective effect of Volvariella volvacea in streptozotocin administered rats

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i4.27707 ◽

2016 ◽

Vol 11 (4) ◽

pp. 903 ◽

Cited By ~ 1

Author(s):

Soosaimanickam Carmel Punitha ◽

Muthu Rajasekaran

Keyword(s):

Advanced Glycation End Products ◽

Glycosylated Hemoglobin ◽

Lipid Peroxides ◽

Protein Carbonyls ◽

Control Group ◽

Volvariella Volvacea ◽

Advanced Glycation ◽

Group I ◽

Glycation End Products ◽

End Products

The present study examined the cardioprotective role of methanol extract of the edible mushroom Volvariella volvacea against oxidative stress in hyperglycemic rats. Rats divided into 6 groups were administered with nicotinamide and streptozotocin intraperitoneally, except Group I (control). Group II served as diabetic control. Group III was given glibenclamide. Two groups (IV and V) of rats received (200 and 400 mg/kg) mushroom extracts orally for 30 days and Group VI received vitamin E (40 mg/kg). After the treatment period, lipid peroxides, carbonyl end products, advanced glycation end products, reduced glutathione, glutathione peroxidase, glutathione-S transferase, catalase, superoxide dismutase and non-enzymatic anti-oxidants (vitamin C and E) were assessed in the heart tissues of experimental animals. Glycosylated hemoglobin was estimated in blood. Electrocardiography recordings of the treated groups were also done. The results showed that mushroom extract treatment reduced the lipid peroxides, advanced glycation end products and protein carbonyls significantly and reversed the altered anti-oxidant enzymes, and the vitamins.Video Clips:<a href="https://www.youtube.com/v/wn01m31-XhY">Hemolysate preparation</a>: 2 min 50 sec<a href="https://www.youtube.com/v/B0OLbU-NdEM">Mixing, glycosylated hemoglobin separation and reading absorbance</a>: 3 min 10 sec

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

Nutrients ◽

10.3390/nu13010080 ◽

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.

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Role of Advanced Glycation End Products in Assessment of Diabetes Mellitus as a Risk Factor for Retinal Vein Occlusion

Applied Sciences ◽

10.3390/app11177934 ◽

2021 ◽

Vol 11 (17) ◽

pp. 7934

Author(s):

Karolina Kaźmierczak ◽

Paweł Żuchowski ◽

Katarzyna Łapińska-Duczmal ◽

Katarzyna Zabel ◽

Zofia Sikorska ◽

...

Keyword(s):

Diabetes Mellitus ◽

Retinal Vein Occlusion ◽

Advanced Glycation End Products ◽

Systemic Hypertension ◽

Control Group ◽

Skin Autofluorescence ◽

Advanced Glycation ◽

Vein Occlusion ◽

Glycation End Products ◽

End Products

Aim: In this study, we aimed to assess the correlation between diabetes mellitus (DM) and the retinal vein occlusion (RVO) based on skin autofluorescence (SAF) measurement, which reflects the accumulation of advanced glycation end products (AGE) in patients who have undergone an episode of central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Material and methods: In total, 23 patients (16 males, 7 females) with RVO were included in this study. Among these 23 participants, 12 (52%) had been diagnosed with CRVO and 11 (48%) with BRVO. The control group consisted of 14 healthy volunteers (11 females, 3 males). To calculate the risk of cardiovascular diseases (CVD) and DM, we conducted SAF examinations. We compared the SAF levels in three groups of patients: (1) with CRVO, (2) with BRVO, and (3) the control group. Basic demographic and clinical information and detailed history of the concurrent diagnoses of systemic diseases, such as systemic hypertension (HTN), DM, hyperlipidemia (HL), and heart diseases, were obtained. Results: In total, 10 (43.5%) patients were diagnosed with DM, 6 (55%) in the BRVO group and 4 (33%) in the CRVO group. The mean SAF value was significantly higher in the BRVO group than in the control group (2.64 a.u. and 2.35 a.u., respectively) (p = 0.023). More patients with risk of DM were identified in the CRVO group than in the BRVO group (p = 0.024). Conclusions: The advanced glycation end products (AGE) in the skin autofluorescence (SAF) is a viable method of evaluating the risk of DM in patients with RVO. We confirmed a correlation between RVO and DM, which was significantly pronounced in the CRVO form, although further carefully devised studies on the relationship between RVO and DM with a larger number of responders should be conducted in the future.

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THE EXTRACT SOYBEAN OF LOCAL VARIETIES AS REDUCE ADVANCED GLYCATION END PRODUCTS AND HEMOGLOBIN A1C IN TYPE 2 DIABETES MICE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i11.26513 ◽

2018 ◽

Vol 11 (11) ◽

pp. 333 ◽

Cited By ~ 1

Author(s):

Juliana Christyaningsih ◽

Taufiqurrahman Taufiqurrahman ◽

Sujono Sujono

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Advanced Glycation End Products ◽

Hemoglobin A1c ◽

Control Group ◽

Advanced Glycation ◽

Local Varieties ◽

Glycation End Products ◽

End Products

Objectives: Glucose and amino acids or fat in diabetic patients if were oxidized to form a compound amadori product (hemoglobin A1c [HbA1c]) and intermediate dicarbonyl that uses reactive carbonyl groups to bind with the amino acids to form advanced glycation end products (AGEs). Soybean is classified as a low index glycemic and content of polyphenol compounds are reported to have various biological activities, which are beneficial to health. Project objectives: The aim of this study was to determine the effect of extract soybean of local varieties obtained on AGEs and HbA1c.Methods: This study was a randomized pretest-posttest control group design. The amount of 28 Mus musculus Balb/C was divided into seven groups. The control group was divided four, while the test group was given extracts of three varieties of soybean, that is, Gema, Wilis, and Argomulyo at a dose equivalent to 1 g of soy/kg BW/day for 25 days. Type 2 diabetes (T2D) mice made with the administration of STZ at a dose of 55 mg/kg in mice.Results: There is a sign of differences in HbA1c levels in the group of mice, and there are different levels of AGEs, though not statistically significant in the group of mice.Conclusions: The extract soybean was a positive effect on the levels of AGEs and HbA1c in T2D mice.

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The Relationship between Plasma Soluble Receptor for Advanced Glycation End Products and Coronary Artery Disease

Disease Markers ◽

10.1155/2019/4528382 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Xiangming Wang ◽

Tingting Xu ◽

Deeraj Mungun ◽

Chuanwei Zhou ◽

Zhimin Zha ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Advanced Glycation End Products ◽

Plasma Levels ◽

Control Group ◽

Syntax Score ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Artery Disease

Background. Inflammation is involved in the development and progression of coronary artery disease (CAD). The role of the receptor for advanced glycation end products (RAGE) in the development of CAD has been recognized. The expression of sRAGE and S100A12 in patients with coronary artery disease from different studies was inconsistent. We attempted to determine the expression of sRAGE and S100A12 and their relationship in the subjects with different severity levels of CAD. Methods. A total of 259 patients undergoing coronary angiography were enrolled from the Department of Geriatric Cardiology in the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2016. Groups were divided as follows: normal coronary artery (control group), nonobstructive coronary atherosclerosis (<50% stenosis in all coronary vessels, NOCA group), stable angina (SAP group), and acute coronary syndrome (ACS group). During CAG or PCI, peripheral arterial blood was collected from all the patients. Plasma sRAGE and S100A12 levels were measured by ELISA. We calculated the SYNTAX score of each patient with CAD according to the result of CAG. Results. The levels of sRAGE were significantly elevated in the ACS group compared with those in the control group, the NOCA group, and the SAP group. sRAGE levels were similar among the control group, the NOCA group, and the SAP group. Plasma S100A12 levels were significantly higher in the ACS group than in the control group and the NOCA group. Baseline correlations between plasma levels of sRAGE and plasma S100A12 in the ACS group were significant. Plasma sRAGE concentration was increasing in patients with ACS and was significantly positively correlated with the increasing SYNTAX score. ROC curve analysis revealed that the combination of sRAGE and S100A12 had a good performance in the prediction of high-risk CAD patients. Conclusion. The plasma levels of sRAGE and S100A12 can be increased in patients with ACS. The elevated sRAGE concentration may be independently associated with the severity of CAD and the inflammatory process. sRAGE combined with S100A12 may be used as a predictor of severe coronary heart disease.

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Advanced Glycation End-Products (AGEs) and Their Soluble Receptor (sRAGE) in Women Suffering from Systemic Lupus Erythematosus (SLE)

Cells ◽

10.3390/cells10123523 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3523

Author(s):

Agnieszka Nowak ◽

Brygida Przywara-Chowaniec ◽

Aleksandra Damasiewicz-Bodzek ◽

Dominika Blachut ◽

Ewa Nowalany-Kozielska ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Advanced Glycation End Products ◽

Lupus Erythematosus ◽

Soluble Form ◽

Control Group ◽

Advanced Glycation ◽

Systemic Lupus ◽

Serum Samples ◽

Glycation End Products ◽

End Products

Systemic lupus erythematosus (SLE) is characterized by abnormal action of the immune system and a state of chronic inflammation. The disease can cause life-threatening complications. Neoepitopes arising from interdependent glycation and oxidation processes might be an element of SLE pathology. The groups included in the study were 31 female SLE patients and 26 healthy female volunteers (the control group). Blood serum samples were obtained to evaluate concentrations of advanced glycation end-products (AGEs), carboxymethyllysine (CML), carboxyethyllysine (CEL), pentosidine, and a soluble form of the receptor for advanced glycation end-products (sRAGE). Compared to a healthy control group, the SLE patients exhibited a higher concentration of AGEs and a lower concentration of sRAGE in serum. There were no statistically significant differences in serum CML, CEL, and pentosidine concentrations between the groups. Therefore, SLE patients could be at risk of intensified glycation process and activation of the proinflammatory receptor for advanced glycation end-products (RAGE), which could potentially worsen the disease course; however, it is not clear which compounds contribute to the increased concentration of AGEs in the blood. Additionally, information about the cigarette smoking and alcohol consumption of the study participants was obtained.

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