Ask about this productRelated genes to: SLC22A12 antibody
- Gene:
- SLC22A12 NIH gene
- Name:
- solute carrier family 22 member 12
- Previous symbol:
- -
- Synonyms:
- OAT4L, RST, URAT1
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-07-31
- Date modifiied:
- 2016-02-18
Related products to: SLC22A12 antibody
Related articles to: SLC22A12 antibody
- Impaired renal urate excretion is a major mechanism underlying hyperuricemia and gout, with urate transporter 1 (URAT1), encoded by SLC22A12, playing a central role in proximal tubular urate reabsorption. This review summarizes the biological relevance of URAT1, the pharmacological evolution of URAT1 inhibitors, and their clinical implications in urate-lowering therapy. Evidence from transporter biology, structural pharmacology, pharmacokinetic and pharmacodynamic studies, and clinical trials was narratively synthesized. URAT1 inhibitors lower serum urate by blocking renal tubular urate reabsorption and increasing urinary urate excretion, providing a mechanism complementary to xanthine oxidase inhibition. Early uricosuric agents established the clinical value of this approach but are limited by non-selective transporter inhibition, tolerability concerns, drug-drug interactions, and organ-specific safety issues. Newer selective URAT1 inhibitors have been developed to improve transporter selectivity, pharmacodynamic precision, and clinical usability. Current evidence supports selective URAT1 inhibition as an effective strategy for achieving serum urate targets, particularly in underexcretion-type hyperuricemia, while renal monitoring and prevention of uric acid stone formation remain important. Emerging agents may further expand treatment options, but long-term renal, hepatic, and cardiovascular safety require further validation. Overall, URAT1 inhibition represents a rational and increasingly precise therapeutic strategy for hyperuricemia and gout, with future research needed to define its long-term outcomes, comparative effectiveness, pharmacogenomic predictors, and broader cardio-renal-metabolic implications. - Source: PubMed
Publication date: 2026/08/17
Li GuangtaoWang YuZhang Zhuoli - Renal fibrosis is a central pathological process in chronic kidney disease (CKD). Although Haikun Shenxi Capsule (HKSX) has shown clinical efficacy in CKD, its precise molecular targets and mechanisms remain unclear. - Source: PubMed
Gu MingjiaYang LeXu AnjingBao NengNi YingCao FangGu XuejingWen KejianCheng Xiaolan - Hyperuricemia (HUA) is primarily attributed to insufficient uric acid (UA) excretion. 6'‑O‑Caffeoylarbutin (CA), the primary bioactive constituent of anti‑gout herbal tea (Que Zui tea), has demonstrated potential urate‑lowering effects; however, its underlying mechanisms require further elucidation. In the present study, a hypoxanthine (HX) and potassium oxonate (PO) induced hyperuricemia (HUA) mouse model was established to assess the effects of different doses of CA. Biochemical analyses, histopathological examination, western blotting and 16S rRNA gene sequencing were conducted to explore the underlying mechanisms. Notably, CA markedly reduced serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and alleviated renal and intestinal histopathological damage. In the kidney, CA upregulated ATP‑binding cassette sub‑family G member 2 (ABCG2), and downregulated glucose transporter 9 (GLUT9) and urate transporter 1 expression (URAT1). In the intestine, CA increased ABCG2, PDZ domain containing 1 (PDZK1) and tight junction protein expression, while decreasing GLUT9, suggesting improved urate excretion and barrier integrity. 16S ribosomal RNA sequencing revealed that CA was associated with increased gut microbial diversity and reduced abundance of potentially harmful bacteria, including . Phylogenetic Investigation of Communities by Reconstruction of Unobserved States‑based prediction suggested accompanying shifts in microbial functions related to transport and metabolism. In conclusion, these findings suggested that CA may exert beneficial effects on HUA involving regulation of renal and intestinal urate transport, improvement of intestinal barrier function and favorable modulation of gut microbiota. CA may therefore serve as a potential candidate for functional food development or therapeutic strategies against HUA. - Source: PubMed
Publication date: 2026/08/21
Yu XuezhiZhang YangSun KonchunYang RuiLi XingdeChen XiuzhenLi TiantianYang XiaoleiLi MingLiu LuLi FeiShen Baochun - Hyperuricemia (HUA) is a common metabolic disorder with limited safe and effective therapeutic options. This study integrated GEO dataset mining and network pharmacology to explore the anti-HUA efficacy and mechanism of pomegranate peel polyphenol extract (PPE). In a mouse model of HUA induced by potassium oxonate and 5% fructose water, PPE significantly reduced serum, urinary, and fecal uric acid levels, attenuated the increases in creatinine and blood urea nitrogen, improved estimated glomerular filtration rate, and ameliorated renal pathological damage, inflammation, and xanthine oxidase activity. Integration of GEO-derived HUA-related genes and computational target prediction for PPE identified 44 common targets, and protein-protein interaction network analysis revealed core targets including Akt1. KEGG enrichment highlighted the PI3K-AKT signaling pathway as a key mediator. Western blotting in vivo and in vitro confirmed that PPE suppressed PI3K-AKT phosphorylation and downregulated the urate reabsorption transporters URAT1 and GLUT9. Furthermore, experiments in UA-induced HK-2 cells demonstrated that ellagic acid, a major bioactive component of PPE, acted through the same pathway. These findings indicate that PPE reduces uric acid levels and protects the kidney via modulation of the PI3K-AKT pathway, providing an integrative data-driven rationale for its potential as a functional food or pharmaceutical agent against HUA. - Source: PubMed
Yin ZeyuLiang ShufeiYang GangaoGuo PingpingWang ChaoHan QingqingSong Xinhua - Urate transporter 1 (URAT1, encoded by SLC22A12) is a key mediator of renal urate reabsorption and an important pharmacological target for urate-related disorders. Sodium butyrate (BuNa), a gut microbiota derived short-chain fatty acid, has been implicated in host metabolic regulation, but its role in renal urate transport remains unclear. Here, using molecular docking, cellular thermal shift assays, immunoprecipitation-mass spectrometry and multi-omics analyses, we identified free fatty acid receptor 2 (FFAR2) as a direct target of BuNa in renal proximal tubular HK2 cells . BuNa binding upregulated FFAR2 and promoted URAT1 expression and urate uptake via an FFAR2-dependent pathway. Mechanistically, BuNa/FFAR2 signaling acts via GNAQ to activate PLCβ, generating diacylglycerol and engaging a PKC-dependent p38 MAPK/ELK1 cascade that upregulates arrestin beta 2 (ARRB2). ARRB2 directly binds to IκB, preventing its phosphorylation-dependent degradation, thereby stabilizing IκB and inhibiting NF-κB nuclear translocation. Within the SLC22A12 promoter, NF-κB (RELA/p50) and hepatocyte nuclear factor 1 beta (HNF1β) compete for overlapping binding sites. By blocking NF-κB nuclear entry, BuNa relieves this competition, permitting HNF1β-driven SLC22A12 transcription. Thus, BuNa enhances URAT1-mediated urate reabsorption in HK2 cells via an FFAR2/GNAQ/p38 MAPK/ELK1/ARRB2 axis that stabilizes IκB, suppresses NF-κB, and relieves the competitive binding between NF-κB and HNF1β on the SLC22A12 promoter. These findings establish a previously unrecognized gut microbiota-kidney axis linking microbial BuNa to renal urate homeostasis through a novel transcriptional regulatory circuit. - Source: PubMed
Publication date: 2026/08/03
Cao ChengSun MubinLi JiabaoYuan ZhenyuGu YuweiShao YufanWang LishengJin XiaohuaCheng YijieFan Bo