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Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

Cited 29 time in Web of Science Cited 33 time in Scopus
Authors
Chung, S. S.; Choi, H. H.; Kim, K. W.; Cho, Y. M.; Lee, H. K.; Park, K. S.
Issue Date
2005
Publisher
Springer Verlag
Citation
Diabetologia 48(6):1150-1158
Keywords
3T3 CellsAdipocytes/metabolismAnimalsBase SequenceCell LineDNA FragmentationDNA Primers*Gene Expression RegulationHeat-Shock Proteins/*metabolismHormones, Ectopic/*genetics/metabolismHumansMiceMonocytes/metabolismPlicamycin/analogs & derivatives/pharmacology*Polymorphism, Genetic*Promoter Regions, GeneticRecombinant Fusion Proteins/metabolismResistin
Abstract
AIMS/HYPOTHESIS: Resistin is an adipokine that might link obesity and insulin resistance. A common polymorphism of the human resistin gene, -420C >G, is a major determinant of plasma resistin concentrations as well as resistin mRNA expression in human adipose tissue. In this study, we investigated the regulatory mechanism by which this polymorphism affects resistin expression. METHODS: Electrophoretic mobility shift assay was performed to identify the transcription factors binding to the -420G region. Transient transfection and reporter assay were used to measure promoter activities of the resistin gene. The binding ability of stimulatory protein 1 (Sp1) in response to adipocyte differentiation or high glucose concentrations was also measured. RESULTS: Sp1 and stimulatory protein 3 (Sp3) specifically bound to the region around -420G of the human resistin gene. Overexpression of Sp1 increased the promoter activity regardless of -420 genotypes, while the promoter activity of the -420G construct was two-fold higher than that of the -420C construct. In contrast, overexpression of Sp3 scarcely increased the promoter activity. The binding ability of Sp1 to the -420G region was increased in response to adipocyte differentiation. Mithramycin A, an inhibitor of DNA binding of Sp1, reduced the effect of high glucose on transcription induction of the resistin gene in adipocytes. CONCLUSIONS/INTERPRETATION: These results suggest that Sp1 is an important factor regulating transcription of human resistin gene. A common polymorphism of the human resistin promoter, -420C >G, is critical for the binding of Sp1 and modulates the transcriptional activity of the resistin gene by changing the binding ability of Sp1. In addition, Sp1 may be involved in the increase of resistin expression by hyperglycaemia.
ISSN
0012-186X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15864531

http://hdl.handle.net/10371/23037
DOI
https://doi.org/10.1007/s00125-005-1762-y
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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