scholarly journals StoneMod: a database for kidney stone modulatory proteins with experimental evidence

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Supatcha Sassanarakkit ◽  
Paleerath Peerapen ◽  
Visith Thongboonkerd

Abstract Better understanding of molecular mechanisms for kidney stone formation is required to improve management of kidney stone disease with better therapeutic outcome. Recent kidney stone research has indicated critical roles of a group of proteins, namely ‘stone modulators’, in promotion or inhibition of the stone formation. Nevertheless, such information is currently dispersed and difficult to obtain. Herein, we present the kidney stone modulator database (StoneMod), which is a curated resource by obtaining necessary information of such stone modulatory proteins, which can act as stone promoters or inhibitors, with experimental evidence from previously published studies. Currently, the StoneMod database contains 10, 16, 13, 8 modulatory proteins that affect calcium oxalate crystallization, crystal growth, crystal aggregation, and crystal adhesion on renal tubular cells, respectively. Informative details of each modulatory protein and PubMed links to the published articles are provided. Additionally, hyperlinks to other protein/gene databases (e.g., UniProtKB, Swiss-Prot, Human Protein Atlas, PeptideAtlas, and Ensembl) are made available for the users to obtain additional in-depth information of each protein. Moreover, this database provides a user-friendly web interface, in which the users can freely access to the information and/or submit their data to deposit or update. Database URL:https://www.stonemod.org.

2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Yasuhiko Ito ◽  
Takahiro Yasui ◽  
Kazuhiro Niimi ◽  
Shoichiro Iwatsuki ◽  
Takashi Hamakawa ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Suchitra Sutthimethakorn ◽  
Visith Thongboonkerd

Abstract Background and Aims Hyperuricosuria is well documented to get involved in the pathogenesis of kidney stone disease, especially uric acid (UA) and calcium oxalate (CaOx) types. Nevertheless, hyperuricosuria-induced alterations in renal tubular cells and cascade mechanisms that subsequently trigger kidney stone formation remained largely unknown. This study aimed to examine changes in cellular proteome and function in renal tubular cells after treatment with high-dose UA. Method MDCK cells were incubated with 3.5 mM uric acid for 48-h. Cellular proteins were extracted and subjected to quantitative proteomics analysis using 2-D PAGE followed by nanoLC-ESI-ETD MS/MS. The proteome data were confirmed by Western blotting, whereas functional analyses were performed using various assays. Results Quantitative proteomics analysis revealed significant changes in levels of 22 proteins in the UA-treated cells that were related to ATPase activity, mitochondrial transport, cell adhesion and molecule binding, cell projection organization and maintenance of location network, metabolic process, response to unfold proteins, and vesicle-mediated transport. Western blotting confirmed changes in levels of cellular proteins identified by quantitative proteomics. Functional assays revealed an increase in intracellular ATP level and enhancement of tissue repair capability in the UA-treated cells. Interestingly, isolation/purification of apical membranes followed by Western blotting showed the increased levels of HSP70 and HSP90 (the known receptors for CaOx crystals) on apical membranes of the UA-treated cells. CaOx crystal-cell adhesion assay revealed significant increase in CaOx-binding capability of the UA-treated cells, whereas neutralization of the surface HSP70 and HSP90 using their specific monoclonal antibodies caused significant reduction in such binding capability (even below the basal level). Conclusion These findings highlighted changes in renal tubular cells in response to high-dose UA that might be related to the pathogenic mechanisms of kidney stone disease associated with hyperuricosuria.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 13-13
Author(s):  
Chanettee Chanthick ◽  
Visith Thongboonkerd

Abstract Objectives Hyaluronic acid (HA), a large non-sulfated glycosaminoglycan, is one of the major components of extracellular matrix (ECM) in connective tissues and other organs. Currently, it is widely used as a dietary supplement, especially for treatment or prevention of aging-related disorders. On the other hand, HA has been reported with an increased risk of kidney stone disease, particularly calcium oxalate (CaOx) type, but with unclear mechanisms. We therefore performed systematic analyses for its modulatory effects on CaOx monohydrate (COM) crystal at various steps of kidney stone formation processes. Methods HA at 1, 10, 100, 1000 and 10,000 ng/ml was tested in various assays for COM crystallization, crystal growth, aggregation, crystal-cell adhesion and invasion through ECM. Results COM crystallization and crystal aggregation were not affected by HA at all concentrations. However, HA significantly promoted COM crystal growth and adhesion onto renal tubular cells in a dose-dependent manner. Interestingly, COM crystal invasion through the ECM was dramatically enhanced by HA even at very low concentration (such as 1 ng/ml). Conclusions Our findings provide evidence for promoting effects of HA on COM crystal growth, adhesion on renal tubular cell surface and invasion through the ECM, all of which are the important steps for kidney stone formation. Funding Sources TRF-IRN grant.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1917
Author(s):  
Roswitha Siener

The prevalence of kidney stone disease is increasing worldwide. The recurrence rate of urinary stones is estimated to be up to 50%. Nephrolithiasis is associated with increased risk of chronic and end stage kidney disease. Diet composition is considered to play a crucial role in urinary stone formation. There is strong evidence that an inadequate fluid intake is the major dietary risk factor for urolithiasis. While the benefit of high fluid intake has been confirmed, the effect of different beverages, such as tap water, mineral water, fruit juices, soft drinks, tea and coffee, are debated. Other nutritional factors, including dietary protein, carbohydrates, oxalate, calcium and sodium chloride can also modulate the urinary risk profile and contribute to the risk of kidney stone formation. The assessment of nutritional risk factors is an essential component in the specific dietary therapy of kidney stone patients. An appropriate dietary intervention can contribute to the effective prevention of recurrent stones and reduce the burden of invasive surgical procedures for the treatment of urinary stone disease. This narrative review has intended to provide a comprehensive and updated overview on the role of nutrition and diet in kidney stone disease.


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