Nucleosome positioning and gene regulation of the SGLT2 gene in the renal proximal tubular epithelial cells

Hiroaki Takesue, Takeshi Hirota, Mami Tachimura, Ayane Tokashiki, Ichiro Ieiri

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Filtered glucose is mostly reabsorbed by sodium-glucose cotransporter 2 (SGLT2) in the proximal tubules. SGLT2 is predominantly expressed in the human kidney. However, the regulatory mechanisms for SGLT2 gene expression in the human kidney remain unclear. We in this work elucidated the transcriptional regulatory mechanisms for the SGLT2 gene by nucleosome occupancy in the SGLT2 promoter region. Expressions of SGLT2 mRNA and protein were markedly weaker in human kidney-derived HK-2 cells than the human kidney. The nucleosome occupancy level in the SGLT2 promoter region was low in the kidney, but high in HK-2 cells. A treatment with a histone deacetylase inhibitor trichostatin A (TSA) decreased nucleosome occupancy in the promoter region and increased SGLT2 expression levels in HK-2 cells. The upregulation of SGLT2 expression by histone acetylation was accompanied by a higher binding frequency of hepatocyte nuclear factor (HNF) 1a, a transcriptional modulator of SGLT2 in the human kidney, to the promoter region. The transfection of a HNF1a expression plasmid into HK-2 cells resulted in the upregulation of SGLT2 mRNA expression in the presence of TSA, but not in the treatment of dimethylsulfoxide as a control. Nucleosome occupancy in the promoter region was markedly higher in the liver and small intestine than the kidney. Our results indicate that tissue-specific nucleosome occupancy plays an important role in the regulation of SGLT2 gene expression via HNF1a binding at the SGLT2 promoter region.

元の言語英語
ページ(範囲)953-962
ページ数10
ジャーナルMolecular Pharmacology
94
発行部数3
DOI
出版物ステータス出版済み - 9 1 2018

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Sodium-Glucose Transport Proteins
Nucleosomes
Epithelial Cells
Kidney
Genes
Genetic Promoter Regions
trichostatin A
Up-Regulation
Hepatocyte Nuclear Factors
Gene Expression
Messenger RNA
Histone Deacetylase Inhibitors
Acetylation
Dimethyl Sulfoxide

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

これを引用

Nucleosome positioning and gene regulation of the SGLT2 gene in the renal proximal tubular epithelial cells. / Takesue, Hiroaki; Hirota, Takeshi; Tachimura, Mami; Tokashiki, Ayane; Ieiri, Ichiro.

:: Molecular Pharmacology, 巻 94, 番号 3, 01.09.2018, p. 953-962.

研究成果: ジャーナルへの寄稿記事

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