ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Meta-analysis of endometrial transcriptome data reveals novel molecular targets for recurrent implantation failure.Journal of assisted reproduction and genetics · 2024Pooled it
- Effects of Xanthine Oxidase Inhibition by Febuxostat on Lipid Profiles of Patients with Hyperuricemia: Insights from Randomized PRIZE Study.Nutrients · 2024Trial
- Serum uric acid is associated with advanced stages in patients with cardiovascular-kidney-metabolic syndrome.Journal of cardiothoracic surgery · 2026Article
- The role of the gut microbiota-uric acid metabolism axis in high-altitude hyperuricemia: dysregulation mechanisms, pathway associations and therapeutic perspectives.Frontiers in microbiology · 2026Review
- Baseline Risk Factors and Predictive Nomogram for Short-Term Persistent Hyperuricemia Following Laparoscopic Sleeve Gastrectomy: A Dual Center Study.Obesity surgery · 2025Article
- The association between the uric acid to high-density lipoprotein cholesterol ratio (UHR) index and obesity in postmenopausal women: a cross-sectional analysis based on the NHANES.Lipids in health and disease · 2025Article
- The Long-Term Effects of the Selective Inhibitor of Urate Transporter 1, Dotinurad, on Metabolic Parameters and Renal Function in Japanese Patients With Asymptomatic Hyperuricemia.Journal of clinical medicine research · 2025Article
- Sex-specific associations between blood urea nitrogen and risk of hyperuricemia in U.S. adults: the NHANES 1999-2020.Frontiers in endocrinology · 2025Article
- Recent Advances on the Regulations of Organic Anion Transporters.Pharmaceutics · 2024Review
- Identification of three distinct cell populations for urate excretion in human kidneys.The journal of physiological sciences : JPS · 2024Article
- URAT1 is expressed in cardiomyocytes and dotinurad attenuates the development of diet-induced metabolic heart disease.iScience · 2023Article
- Susceptibility genes of hyperuricemia and gout.Hereditas · 2022Review
- Urate transport in health and disease.Best practice & research. Clinical rheumatology · 2021Review
- 27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The estrogen receptor and metabolism.Women's health (London, England)Review
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
The excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been unknown. Here, we show that cholesterol metabolite 27-hydroxycholesterol (27HC) upregulates the uric acid reabsorption transporter URAT1 encoded by SLC22A12 via estrogen receptors (ER). Transcriptional motif analysis showed that the SLC22A12 gene promoter has more estrogen response elements (EREs) than other uric acid reabsorption transporters such as SLC22A11 and SLC22A13, and 27HC-activated SLC22A12 gene promoter via ER through EREs. Furthermore, 27HC increased SLC22A12 gene expression in human kidney organoids. Our results suggest that in hypercholesterolemic conditions, elevated levels of 27HC derived from cholesterol induce URAT1/SLC22A12 expression to increase uric acid reabsorption, and thereby, could increase serum uric acid levels.
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