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LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
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27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action
Masaya Matsubayashi1, Yoshihiko M Sakaguchi1, Yoshiki Sahara2,3
1Department of Future Basic Medicine, Nara Medical University, Nara, Japan.
Summary
Cholesterol metabolite 27HC increases uric acid reabsorption by upregulating the URAT1 transporter via estrogen receptors. This finding links hypercholesterolemia to elevated serum uric acid levels.
Area of Science:
- Nephrology
- Endocrinology
- Metabolic Syndrome Research
Background:
- Uric acid homeostasis is regulated by renal transporters.
- Metabolic syndrome is linked to decreased uric acid excretion, but mechanisms are unclear.
- Cholesterol's specific impact on uric acid transporters remains largely unknown.
Purpose of the Study:
- To elucidate the mechanism by which cholesterol affects uric acid transporters.
- To investigate the role of 27-hydroxycholesterol (27HC) in regulating URAT1 (SLC22A12) expression.
- To determine the involvement of estrogen receptors (ER) in this process.
Main Methods:
- Transcriptional motif analysis of the SLC22A12 gene promoter.
- Investigating 27HC activation of the SLC22A12 promoter via ER and estrogen response elements (EREs).
- Measuring SLC22A12 gene expression in human kidney organoids treated with 27HC.
Main Results:
- The SLC22A12 gene promoter contains more EREs compared to SLC22A11 and SLC22A13.
- 27HC activates the SLC22A12 promoter through ER and EREs.
- 27HC significantly increased SLC22A12 gene expression in human kidney organoids.
Conclusions:
- Elevated 27HC in hypercholesterolemia induces URAT1/SLC22A12 expression.
- This induction increases uric acid reabsorption in the kidneys.
- The findings suggest a mechanism linking cholesterol metabolism to elevated serum uric acid levels.
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