Kidney Stone Microbiome
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ABSTRACT:
PROVIDER: PRJEB39576 | ENA |
REPOSITORIES: ENA
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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: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:Kidney stone disease is influenced by multiple factors, including but not limited to age, gender, genetic background, hydration status, diet and drug. Regarding the gender, epidemiologic data across the world has shown that females at the reproductive age (15-49 years) have lower incidence/prevalence of kidney stone disease approximately 1.5-2.5 folds as compared to males at the same age. However, this gap is narrower in the postmenopausal age, whereas the postmenopausal females with higher serum estrogen levels are less likely to have kidney stones. Furthermore, female stone formers (patients with kidney stones) are associated with lower estrogen levels. Therefore, estrogen has been proposed to serve as the protective hormone against kidney stone disease. However, the precise mechanisms underlying such protective effects of estrogen remain unclear and require further investigations. This study thus investigated the effects of estradiol (which is the most prevalent and potent form of estrogen in females at the reproductive age) on cellular proteome of renal tubular cells using a proteomics approach.
2019-09-09 | PXD014768 | Pride
Project description:We conducted a calculi rat model, applied for an integrated proteomic and transcriptomic analysis to characterize the distinct gene expression profiles in calculi oxalate stone formation and its related kidney injury. Six distinct gene clusters were identified according to the consistency of transcriptome and proteome. Gene Ontology and KEGG pathway enrichment was performed to analyze the functions of each sub-group differentially expressed genes. Results showed that the calculi rat kidney was increased expression of injured & apoptotic markers and immune-molecules, and decreased expression of solute carriers & transporters and many metabolic related factors. The present proteotranscriptomic study provided a data resource and new insights for better understanding of the pathogenesis of nephrolithiasis, will hopefully facilitate the future development of new strategies for the recurrence prevention and treatment in patients with kidney stone disease.
2023-05-10 | PXD039169 | Pride
Project description:Assessment of Health-Related Quality of Life in Rare Kidney Stone Formers in the Rare Kidney Stone Consortium - RKSC 6408
| PRJNA514816 | ENA
Project description:Assessment of Health-Related Quality of Life in Rare Kidney Stone Formers in the Rare Kidney Stone Consortium - RKSC 6408
| PRJNA514815 | ENA
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:<p>Genetic and environmental factors play an important role in the etiology of nephrolithiasis. This project will build on and extend our previous efforts (examining environmental risk factors for stone formation) by allowing us to study the risk of stone formation associated with specific genes and gene-environment interactions. We will take advantage of previously collected data in three large cohort studies: Nurses' Health Study I (n=121,000 women), Nurses' Health Study II (n=116,000 women), and Health Professionals Follow-up Study (n=51,000 men). Over a period of 17 to 26 years, information has been collected prospectively on important exposures including diet, family history, body size measures, past medical history, and medications. We have confirmed over 2000 incident cases of kidney stones in each cohort (DK59583, PI Curhan). Further, we have collected 24-hour urine samples from over 4100 stone formers and non-stone formers; the majority of participants have performed two collections. The primary objective of this project is to examine the association between single nucleotide polymorphisms and the 24-hour urinary excretion of stone promoters (calcium and oxalate) and a stone inhibitor (citrate). The secondary objective is to explore the impact of interactions between the genetic factors and dietary factors on 24-hour urinary excretion of relevant lithogenic factors. These findings should provide new insight into regulation of these important factors and also into novel approaches for prevention of stone formation.</p>
| phs000460 | dbGaP
Project description:Heat shock protein 90 (HSP90) is a highly abundant molecular chaperone that interacts with many other intracellular proteins to regulate various cellular processes. However, compositions of the HSP90-interacting complex remain underinvestigated. This study thus aimed to characterize such complex in human embryonic kidney (HEK293T) cells under normal physiologic state using tandem affinity purification (TAP) followed by protein identification using an ultrahigh-resolution tandem mass spectrometer (Qq-TOF MS/MS). A total of 32 proteins, including four forms of HSP90 and 16 novel HSP90-interacting partners, were successfully identified from this complex using TAP control to subtract non-specific binders. Co-immunoprecipitation followed by immunoblotting and immunofluorescence co-staining confirmed the association of HSP90 with known (HSP70, α-tubulin, and β-actin) and novel (vimentin, calpain-1, and importin-β1) partners. Knockdown of HSP90 by small-interfering RNA (siHSP90) caused significant changes in levels of HSP70, α-tubulin, β-actin, vimentin, and calpain-1, all of which are calcium oxalate (CaOx) crystal-binding proteins that play significant roles in kidney stone formation. Moreover, crystal-binding capability was significantly decreased in siHSP90-transfected cells as compared to non-transfected control and siControl-transfected cells. In summary, we report herein a number of novel HSP90-interacting proteins in renal cells and demonstrate the potential role of HSP90-interacting complex in kidney stone formation.
2018-12-17 | PXD011432 | Pride