Characterization and Functional Analysis of the Promoter of RAGE, the Receptor for Advanced Glycation End Products
Open accessAbstract
The receptor for advanced glycation end products, RAGE, is a member of the immunoglobulin superfamily of cell surface molecules differentially expressed on a range of cell types. Ligation of RAGE perturbs homeostatic mechanisms and, potentially, provides a basis for cellular dysfunction in pathologic situations in which its ligands accumulate. To understand factors underlying RAGE expression, we cloned the 5'-flanking region of the RAGE gene and characterized putative regulatory motifs. Analysis of the putative promoter region revealed the presence of three potential NF-kappaB-like and two SP1 binding sites. Transient transfection of vascular endothelial and smooth muscle cells using chimeric 5'-deletion constructs linked to luciferase reporter revealed that the region -1543/-587 contributed importantly to both basal and stimulated expression of the RAGE gene. This region of the RAGE gene contained three putative NF-kappaB-like binding sites and was responsible for increased luciferase activity observed when endothelial or smooth muscle cells were stimulated with lipopolysaccharide. DNase I footprinting assays and electrophoretic mobility shift assay revealed that two of the three NF-kappaB-like binding sites (1 and 2) were likely functional and responsive to stimuli. Upon simultaneous mutation of NF-kappaB-like sites 1 and 2, both basal promoter expression and response to stimulation with LPS, as measured by relative luciferase activity, were significantly diminished. These results point to NF-kappaB-dependent mechanisms regulating cellular expression of RAGE and suggest a means of linking RAGE to the inflammatory response.
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S100A8/A9 is a marker of intestinal inflammation to predict the degree of inflammatory response.
“S100A8/A9 has been recognized as a marker of intestinal inflammation to predict the degree of inflammatory response [8, 9].”
From Inhibition of SPI1 by ADAP Regulates S100A8/A9 Signaling in Macrophages to Control the Development of Colitis (2026) · cites this paper as [8]
The Discussion links LPS-responsive RAGE expression to an inflammatory response, but does not discuss S100A8/A9 as a marker of intestinal inflammation or as a predictor of its degree. Searches for S100A8/A9 and calprotectin did not locate a passage addressing that claim in our copy. (LLM, conf=0.76)
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- Authors
- Li, J., & Schmidt, A. M.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Schmidt, Ann Marie
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-06
- Volume
- 272
- Issue
- 26
- Pages
- 16498-16506
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1984830754
- Cited by
- 525
- References
- 41
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 11 · 2022: 12 · 2021: 18 · 2020: 18 · 2019: 19 · 2018: 22 · 2017: 24 · 2016: 19 · 2015: 30 · 2014: 23 · 2013: 29 · 2012: 31
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG00602)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- RAGE, receptor for advanced glycation end products, promoter regulation, NF-kappaB binding site, Sp1 binding site, 5'-flanking region, lipopolysaccharide stimulation, endothelial cells, vascular smooth muscle cells, inflammation, transcriptional regulation, DNase I footprinting
- MeSH terms
- Receptor for Advanced Glycation End Products, Base Sequence, Binding Sites, Lipopolysaccharides, Molecular Sequence Data, Promoter Regions, Genetic, Receptors, Immunologic, NF-kappa B, TATA Box
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