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ABSTRACT:
PROVIDER: PRJNA921953 | ENA |
REPOSITORIES: ENA
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Project description:Calcium oxalate stones account for over 80% of urinary stones, while the molecular mechanism of its formation is still not completely elucidated. The incidence of hyperoxaluria in calcium oxalate stone formation ranks only second to hypercalciuria. It plays an important role in the pathophysiological process of stone formation. We analyzed miRNA expression profiles between experimental hyperoxaluric rats and normal rats in order to find out the target genes and signaling pathways in the pathogenesis of hyperoxaluria.
2015-08-18 | GSE72135 | GEO
Project description:Kidney stone disease causes significant morbidity and increases health care utilization. The pathogenesis of stone disease is incompletely understood, due in part to the poor characterization of the cellular and molecular makeup of the human papilla and its alteration with disease. In this work, we characterize the human renal papilla in health and calcium oxalate stone disease using single nuclear RNA sequencing, spatial transcriptomics and high-resolution large scale multiplexed 3D and Co-Detection by indexing (CODEX) imaging. We define and localize subtypes of principal cells enriched in the papilla as well as immune and stromal cell populations. We further uncovered an undifferentiated epithelial cell signature in the papilla, particularly during nephrolithiasis.
2023-05-04 | GSE206306 | GEO
Project description:gut microbiota in a Chinese population with renal uric acid stone
| PRJNA754261 | ENA
Project description:Kidney stone disease causes significant morbidity and increases health care utilization. In this dataset, we applied a single-nucleus assay to renal papila samples in order to charachterize the cellular and molecular niches in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.
2023-05-04 | GSE231569 | GEO
Project description:Clinical and animal studies have demonstrated the increasing evidence of oxidative stress in kidney stone disease. Recent findings have shown that the interactions between calcium oxalate (CaOx) crystals and renal tubular cells can promote many cellular events such as cell proliferation, cell death, cellular injury, mitochondrial dysfunction and inflammatory cascade. All of these cellular events are associated with oxidative stress and overproduction of free radicals and reactive oxygen species (ROS) such as superoxide and hydrogen peroxide in renal tubular cells. However, almost all of these references have shown that oxidative stress occurs after the causative crystals have been deposited in the kidney or exposed to renal tubular cells, whereas its primary role as the etiology remained unclear. In this study, we examined effects of oxidative modifications of urinary proteins on CaOx stone formation processes. Urinary proteins were modified by performic oxidation and the presence of oxidatively modified urinary proteins was verified, quantified and characterized by Oxyblot assay and tandem mass spectrometry (nanoLC-ESI-LTQ-Orbitrap-MS/MS). Subsequently, activities of oxidatively modified urinary proteins on CaOx stone formation processes were examined.
2021-11-03 | PXD019360 | Pride
Project description:Randall’s plaque (RP) is the origin of renal calcification on which idiopathic calcium oxalate (CaOx) kidney stones develop. To establish genomic pathogenesis of RP, we performed the microarray analysis for comparing the gene expressions among renal papillary RP and normal tissue of 23 CaOx and 6 calcium phosphate (CaP) stone formers, and normal papillary tissue of 7 control patients. Compare to normal papillary tissue, RP tissue contained up-regulation of lipocalin 2, interleukin 11, prostaglandin-endoperoxide synthase 1, glutathione peroxidase 3, and monocyte to macrophage differentiation, whereas down-regulation of solute carrier family 12 member 1 and sodium leak channel non selective (either > 2.0- or 0.5-fold, p <0.01). The network and toxicity analysis showed these genes had association with activated mitogen-activated protein kinase, Akt/ phosphatidylinositol 3-kinase pathway, and pro-inflammatory cytokines, which caused renal injury and oxidative stress.
2015-10-03 | GSE73680 | GEO
Project description:The association between kidney stone disease and renal fibrosis has been widely explored in recent years but its underlying mechanisms remain far from complete understanding. Using label-free quantitative proteomics (nanoLC-ESI-LTQ-Orbitrap MS/MS), this study identified 23 significantly altered secreted proteins from calcium oxalate monohydrate (COM)-exposed macrophages (COM-MP) compared with control macrophages (Ctrl-MP) secretome. Functional annotation and protein-protein interactions network analysis revealed that these altered secreted proteins were involved mainly in inflammatory response and fibroblast activation. BHK-21 renal fibroblasts treated with COM-MP secretome had more spindle-shaped morphology with greater spindle index. Immunofluorescence study and gelatin zymography revealed increased levels of fibroblast activation markers (α-smooth muscle actin and F-actin) and fibrotic factors (fibronectin and matrix metalloproteinase-9 and -2) in the COM-MP secretome-treated fibroblasts. Our findings indicate that proteins secreted from macrophages exposed to COM crystals induce renal fibroblast activation and may play important roles in renal fibrogenesis in kidney stone disease.
2021-11-03 | PXD027039 | Pride
Project description:Kidney stones (KS) are very common, excruciating, and are associated with tremendous healthcare cost, chronic kidney disease (CKD), and end stage renal disease (ESRD). Most KS are composed of calcium oxalate and very small increases in urine oxalate concentration increase the risk for stone formation. Besides its critical role in the pathogenesis of KS, emerging data suggest that disturbed oxalate homeostasis (hyperoxaluria and/or hyperoxalemia) contributes to CKD progression, CKD - and ESRD-associated cardiovascular diseases, progression of cyst growth in autosomal dominant polycystic kidney disease (ADPKD), and delayed graft function & poor renal allograft survival. This emphasizes the urgent need for plasma and urinary oxalate lowering therapies, and enhancing the bowel’s ability to secrete oxalate may effectively do so. We previously identified Oxalobacter formigenes (O. formigenes)-derived factors secreted in its culture conditioned medium (CM) which stimulated oxalate transport by human intestinal Caco2-BBE (C2) cells and reduced urinary oxalate excretion in hyperoxaluric mice by enhancing colonic oxalate secretion. Given their remarkable therapeutic potential, we now identified several proteins belonging to Sel1-like family as the major O. formigenes-derived secreted factors, and we determined the crystal structures for six proteins to better understand their function. Importantly, Sel1-14-derived small peptides P8 & P9 were identified as the major factors, with P8+9 closely recapitulate the CM’s effects, including acting through the oxalate transporters SLC26A2 & SLC26A6 and PKA activation. P8+9 also stimulate oxalate transport by human ileal and colonic organoids, confirming that these peptides work in human tissues. Collectively, the identification of these small peptides provide a great opportunity for developing a peptide-based novel therapeutic for hyperoxalemia, hyperoxaluria, and related disorders, impacting the outcomes of patients suffering from KS, primary hyperoxaluria, CKD, ADPKD, ESRD, and renal transplant recipients.
2023-07-24 | PXD024992 | Pride
Project description:The present study aims to assess the potential changes in LncRNAs of proximal renal cells in response to the adhesion of calcium oxalate monohydrate (COM) crystals.
2014-04-26 | GSE57111 | GEO
Project description:The present study aims to assess the potential changes in LncRNAs of proximal renal cells in response to the adhesion of calcium oxalate monohydrate (COM) crystals. lncRNA microarray were applied to evaluate the expression of HK-2 cells exposed to COM crystal for 0 and 24 hours.
2014-04-26 | E-GEOD-57111 | biostudies-arrayexpress