Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1265931 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33651856_1.fastq.gz | Fastqsanger.gz | |||
| SRR33651856_2.fastq.gz | Fastqsanger.gz | |||
| SRR33651857_1.fastq.gz | Fastqsanger.gz | |||
| SRR33651857_2.fastq.gz | Fastqsanger.gz | |||
| SRR33651858_1.fastq.gz | Fastqsanger.gz |
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Project description:Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney diseases. Here, we aim to investigate whether and how macrophage integrin αM (ITGAM) contributes to hyperuricemia-related CKD. In vivo, we explored dynamic characteristics of renal tissue in C57BL/6J mice with hyperuricemia-related CKD. By incorporating transcriptomics and phosphoproteomics data, we analyzed gene expression profile, hub genes and potential pathways. In vitro, we validated bioinformatic findings under different conditions with interventions corresponding to core nodes. We found that hyperuricemia-related CKD was characterized by elevated serum uric acid levels, impaired renal function, activation of macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed Itgam as the potential core gene and was associated with focal adhesion signaling. Notably, we confirmed the upregulated expression of macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys. In vitro, through silencing Itgam, inhibiting p-FAK or p-AKT1 phosphorylation, and concurrent inhibiting of p-FAK while activating p-AKT1 all contributed to the modulation of macrophage M2 polarization. Our results indicated targeting macrophage ITGAM might be a promising therapeutic approach for preventing CKD.
2024-06-26 | GSE262687 | GEO
Project description:<p>Hyperuricemia is a prevalent metabolic illness and an established risk factor for gout and chronic renal disease. Present urate-lowering medications are often limited by side effects, highlighting the necessity for innovative strategies. The gut microbiota has a role in urate homeostasis; however, the precise bacterial components and molecular processes involved are largely unidentified. In this study, we demonstrated that a human-derived Limosilactobacillus fermentum strain M5e mitigates hyperuricemia in mice. Both live bacteria and their cell-free conditioned media specifically increased the expression of the colonic urate exporter ABCG2, hence augmenting intestinal urate excretion. Utilizing integrated metabolomics, we discovered 4-guanidinobutyric acid (4-GBA) as the principal active metabolite in the M5e conditioned media. Subsequent analysis demonstrated that 4-GBA directly interacts with and activates the transcription factor HNF4α, promoting its nuclear translocation and selective transactivation of ABCG2. This work clarifies a detailed gut microbiota-to-host route, linking a functioning bacterium and its effector chemical to the control of a host urate transporter, therefore offering a molecular foundation for innovative treatment strategies in hyperuricemia.</p>
2026-01-26 | MTBLS13637 | MetaboLights
Project description:Sunflower (Helianthus annuus L.) calathide is becoming more well-known as a result of its anti-hyperuricemia bioactivity. Aiming at developing anti-hyperuricemic ingredients in sunflower calathide extract (SCE), we were fortunate to discover abietic acid (AA), identified from SCE, has the capacity to inhibit xanthine oxidase activity at low concentrations (IC50 = 10.60 µM and inhibition constant was 193.5 nM) that examined by inhibitor screening experiment in vitro and computer-simulated molecular docking. To further explore the anti-hyperuricemia effects, the UA-stimulated human embryonic kidney (HEK) 293T cells were evaluated as a conceivable model in the current study. The huge amounts of high-throughput sequencing data, which mapping to reference genome, were analyzed by bioinformatics approaches: Weighted Gene Co-Expression Network Analysis (WGCNA) along with Kyoto Encyclopedia of Genes and Genomes (KEGG). Interestingly, the purine metabolism-related genes expressed in the AA treatment were nearly opposite to that of the UA group, indicating negative feedback regulations that AA perhaps contributes to maintain urate homeostasis in the high UA-exposed kidney cellular environment. Here, we consider that HEK293T cells ought to be an achievable in vitro model for UA metabolism research because the PNPase, PRPS1, PRPS2, and RPIA, which participate in UA generation, widely expressed in the untreated 293T cells as well. And AA markedly suppressed the PNPase, PRPS2, and RPIA expressed in UA-stimulated 293T cells, implying inhibitions for UA biosynthesis. As a result, AA not only inhibited xanthine oxidase activity efficiently but also regulated genes PNPase, PRPS2, and RPIA. It is promising to be developed as an inhibitor against hyperuricemia. Therefore, abietic acid, which could be isolated from plants, has the potential for anti-hyperuricemia, and the current study provided a precedent for pharmacology analysis of natural ingredients.
2022-03-11 | GSE198133 | GEO
Project description:Background Currently, it is not possible to predict whether patients with hyperuricemia (HUA) will develop gout and how this progression may be affected by urate-lowering treatment (ULT). Our study aimed to evaluate differences in plasma lipidome between patients with asymptomatic HUA detected < 40 years (HUA<40) and > 40 years, gout patients with disease onset < 40 years (Gout<40) and > 40 years, and normouricemic healthy controls (HC).
Methods Plasma samples were collected from 94 asymptomatic HUA (77% HUA<40) subjects, 196 gout patients (59% Gout<40), and 53 HC. A comprehensive targeted lipidomic analysis was performed to semi-quantify 608 lipids in plasma. Univariate and multivariate statistics and advanced visualizations were applied.
Results Both HUA and gout patients showed alterations in lipid profiles with the most significant upregulation of phosphatidylethanolamines and downregulation of lysophosphatidylcholine plasmalogens/plasmanyls. More profound changes were observed in HUA<40 and Gout<40 without ULT. Multivariate statistics differentiated HUA<40 and Gout<40 groups from HC with an overall accuracy of > 95%.
Conclusion Alterations in the lipidome of HUA and Gout patients show a significant impact on lipid metabolism. The most significant glycerophospholipid dysregulation was found in HUA<40 and Gout<40 patients, together with a correction of this imbalance with ULT.
Keywords LC-MS, Lipidomics, Glycerophospholipids, Hyperuricemia, Gout, Urate-lowering treatment
Study was published and is accessible under this DOI: https://doi.org/10.1186/s13075-023-03204-6
Please cite as follows: Kvasni?ka, A., Friedecký, D., Brumarová, R. et al. Alterations in lipidome profiles distinguish early-onset hyperuricemia, gout, and the effect of urate-lowering treatment. Arthritis Res Ther 25, 234 (2023). https://doi.org/10.1186/s13075-023-03204-6
2023-10-11 | MSV000093082 | MassIVE
Project description:<p>Hyperuricemia (HUA) is a global metabolic disorder characterized by abnormally elevated serum uric acid (UA) (SUA) level, and this study aimed to design a functional fermented beverage based on the urate-lowering probiotic Lactobacillus paracasei N1115 (LP) and Aronia melanocarpa (black chokeberry) (AR). After fermentation, untargeted metabolomics were first conducted to investigate changes in both nonvolatile and volatile metabolites. Subsequently, in vivo experiments confirmed an enhanced anti-HUA activity in the fermented beverage. AR, fermented AR (FAR), and sterilized FAR (FARS) significantly reduced SUA levels (p < 0.05), protected renal function, and alleviated inflammation through the TLR4/MyD88/NF-κB signaling pathway. Additionally, all three of these down-regulated UA-producing enzymes XOD and ADA, as well as urate transporter URAT1. However, the anti-HUA activity of the fermented beverage is generally better than that of AR. Specifically, LP-mediated fermentation enhanced the anti-XOD effect and imparted new GLUT9 inhibitory activity in AR juice. Following gut microbiota and short-chain fatty acid analyses, it was found that the fermented beverage can promote UA metabolism by increasing butyrate levels through feeding its producer Faecalibaculum. Because the anti-HUA patterns of FAR and FARS were almost identical, and no significant colonization of Lactobacillus was observed, the postbiotics may serve as the primary factors contributing to the enhanced anti-HUA activity of the fermented beverage.</p>
2025-11-28 | MTBLS13414 | MetaboLights
Project description:Gegen Qinlian Decoction ameliorates hyperuricemia-induced renal tubular injury via blocking inflammatory signaling pathway.
| PRJNA723135 | ENA
Project description:Different segments of renal tubules have distinct metabolic features and functions, and defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined. We demonstrated that the renal proximal tubule (PT) has high expression of fatty acid and lipid metabolism enzymes, which is transcriptionally upregulated by abundantly expressed peroxisome proliferator-activated receptor (PPAR)/γ to support active lipid metabolism. In contrast, the renal distal tubule (DT) has elevated glycolytic enzyme expression corresponding with high rates of glycolysis, and this increased expression is mediated by abundantly expressed c-Myc. In addition, Nrf2 upregulated glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-dependent malic enzyme 1 expression for NADPH production and antioxidation in the DT. Highly expressed PPARγ transcriptionally enhanced expression of the protease iRhom2 in the PT, which suppressed epidermal growth factor (EGF) expression and secretion, inhibiting EGF receptor activation-dependent glycolytic gene expression and maintaining the low level of glycolysis. PPARγ inhibition reduced iRhom2 expression and increased EGF and GLUT1 expression in the PT in mice, resulting in hypertrophy of renal tubules and inhibited kidney functions, which can be rescued by inhibition of glycolysis via treatment with 2-deoxy-D-glucose. These findings delineate instrumental molecular mechanisms underlying the active lipid metabolism and suppressed glycolysis in the PT and active glycolysis in the DT and reveal critical roles for PPARs and c-Myc in maintaining metabolic homeostasis in the kidney
2018-11-15 | PXD007828 | Pride
Project description:Insufficient leaf photosynthesis promotes sheath NSC transport to the panicle during grain filling. SnRK1 regulates assimilate distribution between plant tissues and organs. However, the mechanism by which SnRK1 regulates sheath NSC transport to the panicle and its response to limited leaf assimilation remain unclear. Here, we performed leaf cutting (LC) at anthesis to simulate insufficient leaf assimilation and set no treatment as a CK. In response to LC, SnRK1 activity increased rapidly, and NSC transport was advanced. Sheath NSCs were not transported in a snrk1a mutant with deficient SnRK1 activity. These results indicated that SnRK1 activity is important for sheath NSC transport. The high correlation of T6P and sucrose and the inhibition of SnRK1 by T6P in sheaths in vitro implied that T6P slightly inhibits SnRK1 activity in rice sheaths in response to sucrose availability. The increase in SnRK1 activity was accompanied by an increase in OsSnRK1a expression and a low sucrose content. Low sucrose signaling increases SnRK1 transcription. Therefore, we speculated that OsSnRK1a expression positively regulates SnRK1 activity in response to low sucrose availability in rice sheaths. Through phosphoproteomics and further PRM verification, 20 phosphosites that depend on SnRK1 and are correlated with NSC transport were obtained. Based on the function of these sites and proteins, we found that SnRK1 regulates starch degradation, sucrose metabolism, phloem transport, sugar transport across tonoplast, and glycolysis via phosphorylation to promote sheath NSC transport. Overall, our results revealed the importance, function and regulatory mechanism of SnRK1 in sheath NSC transport.
2022-03-18 | PXD024670 | Pride