Regulation of the human Na+-glucose cotransporter gene,SGLT1, by HNF-1 and Sp1
Abstract
The Na+-glucose cotransporter ( SGLT1) is expressed primarily by small intestinal epithelial cells and transports the monosaccharides glucose and galactose across the apical membrane. Here we describe the isolation and characterization of 5.3 kb of the 5′-flanking region of the SGLT1 gene by transiently transfecting reporter constructs into a variety of epithelial cell lines. A fragment (nt −235 to +22) of the promoter showed strong activity in the intestinal cell line Caco-2 but was inactive in a nonintestinal epithelial cell line (Chinese hamster ovary). Within this region, three cis-elements, a hepatocyte nuclear factor-1 (HNF-1) and two GC box sites are critical for maintaining the gene's basal level of expression. The two GC boxes bind to several members of the Sp1 family of transcription factors and, in the presence of HNF-1, synergistically upregulate transactivation of the promoter. A novel 16-bp element just downstream of one GC box was also shown to influence the interaction of Sp1 to its binding site. In summary, we report the identification and characterization of the human SGLT1 minimal promoter and the critical role that HNF-1 and Sp1-multigene members have in enhancing the basal level of its transcription in Caco-2 cells.
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An increase in SGLT-1 protein in the apical brush border of enterocytes occurs in a cAMP-dependent manner in response to basolateral signals, and secondary to increased SGLT-1 transcription and stabilization of the SGLT-1 transcript.
“An increase in SGLT-1 protein in the apical brush border of enterocytes occurs in a cyclic AMP (cAMP)-dependent manner in response to transduction of basolateral signals (54,55), and secondary to an increase in SGLT-1 transcription (56) and stabilization (increased half-life) of the 3 ′ -untranslated region of the SGLT-1 transcript (57,58).”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [58]
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“An increase in SGLT-1 protein in the apical brush border of enterocytes occurs in a cyclic AMP (cAMP)-dependent manner in response to transduction of basolateral signals (54, 55), and secondary to an increase in SGLT-1 transcription (56) and stabilization (increased half-life) of the 3-untranslated region of the SGLT-…”
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西村, 公., 藤田, 征., 井田, 昌., 柳町, 剛., 大橋, 夏., 西, 清., 西田, 淳., Morino, K., 卯木, 智., 西, 英., et al. (n.d.) · Institutional Repositories DataBase (IRDB)
- Authors
- Martín, M. G., Wang, J., Solorzano-Vargas, R. S., Lam, J. T., Turk, E., & Wright, E. M.
- Affiliations
- Division of Gastroenterology and Nutrition, UCLA School of Medicine, Los Angeles 90095-1751; and
- University of California, Los Angeles (US)
- Departments of Physiology and Pediatrics,
- ORCID
- Wright, Ernest M.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2000-04-01
- Volume
- 278
- Issue
- 4
- Pages
- G591-G603
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W1868707770
- Cited by
- 77
- References
- 47
- Citations by year
- 2024: 3 · 2023: 2 · 2022: 2 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- John Spoor Broome Library Institutional Repository (California State University) (submittedVersion)
- Funders
- National Institutes of Health (5r01dk044582-09)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 44582)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD034706, HD 34706)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SGLT1, Na+/glucose cotransporter, HNF1, Sp1, Sp1 binding site, promoter regulation, 5'-flanking region, small intestinal epithelial cells, Caco-2 cells, transcriptional activation, intestinal glucose transport
- MeSH terms
- Animals, Base Sequence, Cell Line, Deoxyribonuclease I, DNA-Binding Proteins, Gene Expression Regulation, Multigene Family, Cricetinae, Humans, Membrane Glycoproteins, Molecular Sequence Data, Monosaccharide Transport Proteins, Nuclear Proteins, Promoter Regions, Genetic, Swine, Transcription Factors, Transfection, Sp1 Transcription Factor, CHO Cells, LLC-PK1 Cells, Caco-2 Cells, DNA Footprinting, Sodium-Glucose Transporter 1, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta
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