Protein Expression of Urate Transporters in Renal Tissue of Patients with Uric Acid Nephrolithiasis

Fu, Weihua; Li, Qianwei; Yao, Jiwei; Zheng, Jing; Lang, Lang; Li, Weibing; Yan, Ji

doi:10.1007/s12013-014-9939-y

Cited by 5 publications

(3 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) 15 mediate urate re-absorption from kidney tubule lumen to blood and 16 maintain blood urate homeostasis. Renal URAT1 and GLUT9 are highly 17 expressed in patients with uric acid nephrolithiasis (Fu et al 2014). 18 Organic anion transporter 1 (OAT1) is responsible for urate secretion 19 from the blood across the basolateral membrane of renal proximal 20 tubules into epithelial cells (Eraly et al 2008).…”

mentioning

confidence: 99%

WITHDRAWN: Anti-hyperuricemic action of vaticaffinol, a resveratrol tetramer isolated from Dipterocarpus alatus in hyperuricemic mice

Chen

Yan

et al. 2015

Phytomedicine

View full text Add to dashboard Cite

mentioning

confidence: 99%

WITHDRAWN: Anti-hyperuricemic action of vaticaffinol, a resveratrol tetramer isolated from Dipterocarpus alatus in hyperuricemic mice

Chen

Yan

et al. 2015

Phytomedicine

View full text Add to dashboard Cite

“…URAT1 and GLUT9 are two primary urate transporters mediating uric acid reabsorption in the kidney. The significant increase of URAT1 protein expression was found in renal tissue of patients with uric acid nephrolithiasis [30]. Dysfunctional mutation in GLUT9 could trigger renal hypouricemia type 2 owing to decreased urate absorption [31].…”

mentioning

confidence: 99%

Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3

Yuan

Chen

et al. 2015

Planta Med

View full text Add to dashboard Cite

Emodinol, 1β,3β,23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our research group, has been demonstrated to exhibit uricosuric activity by our previous study. The aim of this study was to evaluate the uricosuric and nephroprotective effects of emodinol and explore its possible mechanisms in potassium oxonate-induced hyperuricemic mice with renal dysfunction. Mice were orally administrated 250 mg/kg of potassium oxonate once daily for 7 consecutive days to induce hyperuricemia with renal dysfunction. Emodinol was given at doses of 25, 50, and 100 mg/kg on the same day 1 h after oxonate treatment, and allopurinol (10 mg/kg) was given as a positive control. After 1 week, serum uric acid, serum creatinine, urine uric acid, urine creatinine, blood urea nitrogen, and hepatic xanthine oxidase activity were determined. The mRNA and protein levels of urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, oncoprotein-induced transcript 3, and organic cation/carnitine transporters in the kidney were detected by real-time polymerase chain reaction and Western blot analysis. In addition, urinary and renal Tamm-Horsfall glycoprotein concentrations were examined by ELISA assays. Emodinol significantly reduced serum urate levels, increased urinary urate levels and fractional excretion of uric acid, and inhibited hepatic xanthine oxidase activity in hyperuricemic mice. Moreover, potassium oxonate administration led to dys expressions of renal urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, and oncoprotein-induced transcript 3 as well as alternations of uromodulin concentrations, which could be reversed by emodinol. On the other hand, treatment of emodinol caused upregulated expressions of organic cation/carnitine transporters, resulting in an improvement of renal function characterized by decreased serum creatinine and blood urea nitrogen levels. Emodinol exhibited hypouricemic and nephroprotective actions by inhibiting xanthine oxidase activity and regulating renal ion transporters and oncoprotein-induced transcript 3, which may be a potential therapeutic agent in hyperuricemia and renal dysfunction.

show abstract

“…Previous studies on SLC22A12 focused on its function as uric acid transporter. Mutations in the SLC22A12 gene are associated with diseases with abnormal serum uric acid levels, including hypouricemia ( 43 , 44 ), hyperuricemia ( 45 – 47 ), gout ( 43 , 45 , 48 ), and nephrolithiasis ( 49 ). Nevertheless, SLC22A12 is not the only uric acid transporter, and it does not transport solely uric acid.…”

Section: Discussionmentioning

confidence: 99%

Low Expression Levels of SLC22A12 Indicates a Poor Prognosis and Progresses Clear Cell Renal Cell Carcinoma

Liu

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 4/5 of all kidney cancers. Accumulation of minor changes in the cellular homeostasis may be one cause of ccRCC. Therefore, we downloaded the RNA sequencing and survival data of the kidney renal cell carcinoma (KIRC) cohort from the Cancer Genome Atlas (TCGA) database. After the univariate and multivariate Cox regression analyses, 19 kidney-specific differentially expressed genes (DEGs) were found. Solute Carrier Family 22 Member 12 (SLC22A12) resulted in an independent prognostic predictor for both overall survival (OS) and disease-free survival (DFS). SLC22A12 expression was lower in tumoral tissue compared to normal tissue. Moreover, patients in the SLC22A12 low expression group had a higher pathological stage and worse survival than the high expression group. Additionally, qRT-PCR assay, immunoblotting test (IBT), and immunohistochemical (IHC) analyses of cancer tissues/cells and the corresponding normal controls verified that SLC22A12 is downregulated in ccRCC. Receiver operator characteristic (ROC) curves showed that the low expression level of SLC22A12 could be a good diagnostic marker for ccRCC (AUC=0.7258; p <0.0001). Gene set enrichment analysis (GSEA) showed that SLC22A12 expression levels are related to metabolism, cell cycle, and tumor-related signaling pathways. GO and KEGG analyses revealed that SLC22A12 transports multiple organic compounds, ions, and hormones and participates in the extracellular structure organization. Furthermore, SLC22A12 over-expression in vitro inhibited the proliferation, migration, and invasion of renal cancer cells by regulating PI3K/Akt pathways. Such effects were reversed when knocking out SLC22A12. In summary, as a transporter for many vital metabolites, SLC22A12 may affect tumor cell survival through its impacts on the mentioned metabolites. In conclusion, this study uncovered that SLC22A12 is a promising prognostic and diagnostic biomarker for ccRCC.

show abstract

Protein Expression of Urate Transporters in Renal Tissue of Patients with Uric Acid Nephrolithiasis

Cited by 5 publications

References 24 publications

WITHDRAWN: Anti-hyperuricemic action of vaticaffinol, a resveratrol tetramer isolated from Dipterocarpus alatus in hyperuricemic mice

WITHDRAWN: Anti-hyperuricemic action of vaticaffinol, a resveratrol tetramer isolated from Dipterocarpus alatus in hyperuricemic mice

Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3

Low Expression Levels of SLC22A12 Indicates a Poor Prognosis and Progresses Clear Cell Renal Cell Carcinoma

Contact Info

Product

Resources

About