Selective protein enrichment in calcium oxalate stone matrix: a window to pathogenesis?

Wesson, Jeffrey A.; Kolbach-Mandel, Ann M.; Davis, Carley; Mandel, Neil S.

doi:10.1007/s00240-019-01131-3

Cited by 22 publications

(20 citation statements)

References 26 publications

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“…***, p < 0.001; **, p < 0.01; *, p < 0.05 theories suggests that the calcium oxalate-induced injury to renal tubular epithelial cells promotes the adherence and acumination of calcium oxalate crystals results in stone formation [27]. Given proteins are the major component of kidney stone organic matrix and considered to play a regulatory function in cell-crystal interactions and lithogenesis inside the kidney [28][29][30][31], we selected immortalized human proximal tubular epithelial cells HK-2 exposure to COM crystals to generate the cell-crystal interaction model and analyzed the altered proteomic landscape in HK-2 cells in response to COM adhesion. In this study, we first systematically screened the DEPs profiles in COM-HK-2 model by TMT-labeled quantitative proteomics analysis.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals

Zhu

et al. 2020

BMC Urol

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Background: Calcium oxalate monohydrate (COM), the major crystalline composition of most kidney stones, induces inflammatory infiltration and injures in renal tubular cells. However, the mechanism of COM-induced toxic effects in renal tubular cells remain ambiguous. The present study aimed to investigate the potential changes in proteomic landscape of proximal renal tubular cells in response to the stimulation of COM crystals. Methods: Clinical kidney stone samples were collected and characterized by a stone component analyzer. Three COM-enriched samples were applied to treat human proximal tubular epithelial cells HK-2. The proteomic landscape of COM-crystal treated HK-2 cells was screened by TMT-labeled quantitative proteomics analysis. The differentially expressed proteins (DEPs) were identified by pair-wise analysis. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEPs were performed. Protein interaction networks were identified by STRING database. Results: The data of TMT-labeled quantitative proteomic analysis showed that a total of 1141 proteins were differentially expressed in HK-2 cells, of which 699 were up-regulated and 442 were down-regulated. Functional characterization by KEGG, along with GO enrichments, suggests that the DEPs are mainly involved in cellular components and cellular processes, including regulation of actin cytoskeleton, tight junction and focal adhesion. 3 high-degree hub nodes, CFL1, ACTN and MYH9 were identified by STRING analysis. Conclusion: These results suggested that calcium oxalate crystal has a significant effect on protein expression profile in human proximal renal tubular epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals

Zhu

et al. 2020

BMC Urol

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“…2 and 3 and Table 6). Those upregulated in the KS group might reflect ongoing subtle inflammation (e.g., CD14, CD40, Endoglin) and injury/matrix remodeling (e.g., Osteopontin, E-selectin, EGFR, PDGFRβ), as has been suggested by others [60][61][62][63][64][65][66]. Downregulation in the NC group (e.g., MCP-1 and OPN) might reflect loss of proximal tubular function and/or cell number, and ultimately contribute to CKD progression.…”

Section: Discussionmentioning

confidence: 61%

Specific populations of urinary extracellular vesicles and proteins differentiate type 1 primary hyperoxaluria patients without and with nephrocalcinosis or kidney stones

Jayachandran

Yuzhakov

Kumar

et al. 2020

Orphanet J Rare Dis

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Background Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process. Methods Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m2 were studied. Urinary EVs were quantified by digital flow cytometer and results expressed as EVs/ mg creatinine. Expressions of urinary proteins were measured by customized antibody array and results expressed as relative intensity. Data were analyzed by ANCOVA adjusting for sex, and biomarkers differences were considered statistically significant among groups at a false discovery rate threshold of Q < 0.20. Results Total EVs and EVs from different types of glomerular and renal tubular cells (11/13 markers) were significantly (Q < 0.20) altered among PH1 patients without NC and KS, patients with NC or patients with KS alone. Three cellular adhesion/inflammatory (ICAM-1, MCP-1, and tissue factor) markers carrying EVs were statistically (Q < 0.20) different between PH1 patients groups. Three renal injury (β2-microglobulin, laminin α5, and NGAL) marker-positive urinary EVs out of 5 marker assayed were statistically (Q < 0.20) different among PH1 patients without and with NC or KS. The number of immune/inflammatory cell-derived (8 different cell markers positive) EVs were statistically (Q < 0.20) different between PH1 patients groups. EV generation markers (ANO4 and HIP1) and renal calcium/phosphate regulation or calcifying matrixvesicles markers (klotho, PiT1/2) were also statistically (Q < 0.20) different between PH1 patients groups. Only 13 (CD14, CD40, CFVII, CRP, E-cadherin, EGFR, endoglin, fetuin A, MCP-1, neprilysin, OPN, OPGN, and PDGFRβ) out of 40 proteins were significantly (Q < 0.20) different between PH1 patients without and with NC or KS. Conclusions These results imply activation of distinct renal tubular and interstitial cell populations and processes associated with KS and NC, and suggest specific populations of urinary EVs and proteins are potential biomarkers to assess the pathogenic mechanisms between KS versus NC among PH1 patients.

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“…Histamine 1 receptors are frequently found inside the ureter and their antagonist (dimenhydrinate) are found helpful in relieving pain caused due to stones (renal colic) and ease the natural elimination of stones by inhibiting renal vasodilators and urethral contractions [27]. PROZ1 (protein Z, vitamin K dependent plasma glycoprotein) is a stone matrix protein but in higher abundance [24,28]. F I G .…”

Section: Hrh1 (Histamine Receptor H1)mentioning

confidence: 99%

Insights into association between urolithiasis and prostate cancer

Sun¹,

Kour²,

Wang³

et al. 2021

JOMH

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Background and objective: Urolithiasis or renal stones form a major urinary tract infection with formation of calciﬁcations in the bladder and uterus. With the lifestyle diseases burgeoning, the renal stones have become a common cause with an approximate 1 in 1000 people affected all over the world with a risk ratio of 3 : 1 in men and women. On the other hand, prostate or genitourinary cancers are well documented to be associated with urolithiasis. Methods: A gene list was prepared from the published NCBI dataset, comprising all the genes related to urolithiasis primarily with mutations (both pathogenic and likely pathogenic Single nucleotide polymorphisms, SNP's) for every particular gene screened later from the published datasets. To see the interactions among all the potential genetic factors, PPI based tools were used and an interaction map was prepared. For the characterization of mutations, we have used gnomAD for verifying all the SNPs whether they are synonymous or nonsynonymous mutations. Results: We outlined the list of genes and discussed the systems bioinformatics integrated approach associated with it. Conclusion: We found a large number of genes common to them and their association is subtly known for immunomodulatory response.

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Selective protein enrichment in calcium oxalate stone matrix: a window to pathogenesis?

Cited by 22 publications

References 26 publications

Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals

Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals

Specific populations of urinary extracellular vesicles and proteins differentiate type 1 primary hyperoxaluria patients without and with nephrocalcinosis or kidney stones

Insights into association between urolithiasis and prostate cancer

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