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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3896

Title: 27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.
Other Titles: 27ヒドロキシコレステロールはエストロゲン受容体を介してヒトSLC22A12の発現を制御する
Authors: Matsubayashi, Masaya
Sakaguchi, Yoshihiko M
Sahara, Yoshiki
Nanaura, Hitoki
Kikuchi, Sotaro
Asghari, Arvand
Bui, Linh
Kobashigawa, Shinko
Nakanishi, Mari
Nagata, Riko
Matsui, Takeshi K
Kashino, Genro
Hasegawa, Masatoshi
Takasawa, Shin
Eriguchi, Masahiro
Tsuruya, Kazuhiko
Nagamori, Shushi
Sugie, Kazuma
Nakagawa, Takahiko
Takasato, Minoru
Umetani, Michihisa
Mori, Eiichiro
Keywords: 27-hydroxycholesterol
estrogen receptor
transcriptional regulatory element
uric acid
Issue Date: Jan-2021
Publisher: Wiley
Citation: FASEB journal Vol.35 No.1 Article No.e21262 (2021 Jan)
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.
Description: 博士(医学)・甲第772号・令和3年3月15日
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
URI: http://hdl.handle.net/10564/3896
ISSN: 08926638
DOI: https://doi.org/10.1096/fj.202002077R
Academic Degrees and number: 24601A772
Degree-granting date: 2021-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2020年度

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