The osteopontin-controlled switching of calcium oxalate monohydrate morphologies in artificial urine provides insights into the formation of papillary kidney stones

Langdon, Aaron; Grohe, Bernd

doi:10.1016/j.colsurfb.2016.06.030

Cited by 15 publications

(17 citation statements)

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“…Tamm-Horsfall protein (THP) was identified as a kidney-specific protein, serve as a key regulator in promoting the aggregation of calcium-salt crystals and stone formation [34,35], which is a potent immunomodulatory molecule and a disease biomarker in the urinary system [35]. Osteopontin (OPN) is another important component of calcium oxalate stone matrix [29], plays an important role in preventing the formation of calcium oxalate monohydrate (COM) kidney stones, which controls switching of calcium oxalate monohydrate morphologies in urine [36] to promote the formation of stones by promoting crystal adhesion and mediating oxidative stress and apoptosis [17,37]. In this study, we identified that the LZTS1 (leucine zipper hypothetical tumor suppressor gene 1) protein, a full-length 596 amino acid protein with a molecular weight of 67 kD, was significantly upregulated in COM adhered HK-2 cells.…”

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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“…As a negatively charged phosphorylated glycoprotein, OPN expressed in bone tissue, and expressed in the kidney, arterial vascular smooth muscle cell, urogenital tract, gallbladder, and other tissues. OPN showed a significant increase in renal expression levels in renal calculi rats [ 37 ], Langdon, A and Grohe, B investigated the interaction of OPN proteins and COM crystals by scanning electron microscopy and confocal microscopy, and found that the key control factor leading to the formation of stones was OPN [ 38 ]. By immunohistochemical method and transmission electron microscopy, Taguchi, K, and others found: OPN in RP expressed higher than the parts of renal tubular epithelial cells that do not contain RP [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The effects of HAP and macrophage cells to the expression of inflammatory factors and apoptosis in HK-2 cells of vitro co-cultured system

Deng

Zhou

et al. 2017

Urolithiasis

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This study developed an in vitro system by co-culturing HK-2 cells with different concentration of hydroxyapatite (HAP) and/or macrophage cells to simulate the internal environment of urolithiasis as far as possible, investigating the regulatory effects of macrophage cells on HAP-induced expression of relative inflammatory factors of HK-2 cells. The control group (H group) was only comprised of HK-2 cells. Experimental groups included co-culturing HK-2 cells and macrophage cells (H + M group), co-culturing HK-2 cells and HAP (H + A group), co-culturing macrophage cells and HAP (M + A group), and co-culturing HK-2 cells and macrophage cells with HAP (H + M + A group). In the H + A, M + A, and H + M + A group, we set the concentration of HAP as 5 μg/cm2 (A1) and 10 μg/cm2 (A2). After co-culturing for 2, 4, and 6 h, we detected the expression of CCL-2 in the liquid by ELISA. We tested the expression of LDH and ROS to evaluate the damage of HK-2 cells. We assessed the apoptosis of HK-2 cells using DAPI staining assay, flow cytometry, and the rate of BAX/BCL-2. Western Blotting detected OPN, Fetuin-A, BAX, and BCL-2 of HK-2 cells. The expression of CCL-2 in the medium of H + A1 and H + A2 group increased significantly compared with the control (P < 0.05); CCL-2 of M + A1 and M + A2 group was higher than the H + A1 and H + A2 group (P < 0.05). The expression of CCL-2 in H + M + A1 and H + M + A2 group was also higher than M + A1 and M + A2 group (P < 0.05). Compared with control, the expression of OPN, LDH release, the ratio of BAX/BCL-2, and the generation of ROS in HK-2 cells increased in a dose- and time-dependent manner. Compared with the control, the expression of Fetuin-A decreased in various degrees at different incubation periods. Especially when co-culturing for 6 h, Fetuin-A decreased most seriously in the H + M + A1 group. (1) The HAP can induce the HK-2 cells oxidative stress and inflammatory damage and apoptosis, when adding the macrophages to co-culture, macrophage cells can aggravate the damage and apoptosis of the HK-2 cells. (2) After the stimulation of HAP, the expression of OPN in HK-2 cells increased in a time- and dose-dependent manner; macrophage cells can aggravate the increase of OPN in HK-2 cells. (3) In the HAP and HK-2 cells co-cultured system, the low-level Fetuin-A of HK-2 cells may be related to the excessive consumption of Fetuin-A in the process of HAP-induced renal tubular epithelial cell excessive oxidative stress, inflammatory injury, and cell apoptosis. When adding macrophage cells to co-culture, Fetuin-A decreased even more seriously, it reminds us that macrophage cells can slightly regulate the expression of Fetuin-A in the HK-2 cells.Electronic supplementary materialThe online version of this article (10.1007/s00240-017-1032-8) contains supplementary material, which is available to authorized users.

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“…9,[39][40][41] The control solutions (without peptide) showed the formation of well-facetted COM, which has a growth habit of layered-platelet structures caused by penetrating twinning of {001} and {100} faces. 12,42 However, the presence of CAP-pip in LIC, induced dramatic morphological changes on COM, showing smaller and fused crystals with disruptions in {100} face. At high magnification, these crystals exhibit steps and pits in their {121} faces.…”

Section: Effects Of Cap-pi and Cap-pip On Calcium Oxalate Crystallimentioning

confidence: 99%

Nucleation and growth inhibition of biological minerals by cementum attachment protein‐derived peptide (CAP‐pi)

Montoya

López

Arenas

et al. 2020

Journal of Peptide Science

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Biomineralization is a highly regulated process where proteins/peptides-crystal interactions contribute to the shaping, phasing and aggregation of minerals. We have identified and synthesized a cementum attachment protein-derived peptide (CAP-pi), which corresponds to amino acids 40-53 of the N-terminal CAP domain (MASSDEDGTNGGAS) and its phosphorylated variant (MASpSpDEDGTNGGASp) (CAP-pip). The peptide is composed of polar and negatively charged amino acids, which are disordered, according to in silico analysis. Our results show that CAP-pi inhibits hydroxyapatite (HA) formation and growth. However, it possesses low capacity to inhibit calcium oxalate crystal growth. CAP-pip showed a stronger inhibitory effect on the formation and growth of HA. As well as a high capacity to inhibit calcium oxalate monohydrate growth, mainly due to adsorption on specific growth faces. Small peptides have many advantages over the full-size protein, including lowcost production and modulation characteristics that allow for structural changes. Our findings suggest that CAP-pip-derived peptide could possess therapeutic potential to prevent or treat pathological calcifications such as renal stones and vascular calcification.

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The osteopontin-controlled switching of calcium oxalate monohydrate morphologies in artificial urine provides insights into the formation of papillary kidney stones

Cited by 15 publications

References 65 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

The effects of HAP and macrophage cells to the expression of inflammatory factors and apoptosis in HK-2 cells of vitro co-cultured system

Nucleation and growth inhibition of biological minerals by cementum attachment protein‐derived peptide (CAP‐pi)

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