Plasminogen activator inhibitor-1 promoter activity in adipocytes is not influenced by the 4 G/5 G promoter polymorphism and is regulated by a USF-1/2 binding site immediately preceding the polymorphic region.
J Mol Endocrinol
; 32(1): 155-63, 2004 Feb.
Article
de En
| MEDLINE
| ID: mdl-14765999
ABSTRACT
Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with obesity indicating that adipocytes influence PAI-1 plasma levels. In addition, the 4 G/5 G promoter polymorphism of the PAI-1 gene may modulate PAI-1 transcription. We investigated the transcriptional regulation of the human PAI-1 gene in adipocytes and analyzed the genetic contribution of the 4 G/5 G polymorphism. The PAI-1 promoter was analyzed using electrophoretic mobility shift assays (EMSAs) and luciferase reporter gene assays. A putative binding site for the upstream stimulatory factor-1/2 (USF-1/2) at the polymorphic region of the PAI-1 promoter was identified. The binding of USF-1/2 was studied using nuclear extracts prepared from adipocytes and was similar in all the promoter variants as analyzed by EMSA. A 257 bp PAI-1 promoter fragment including the 4 G/5 G site was transcriptionally active in adipocytes and was not influenced by the polymorphism. The present data indicate for the first time that USF-1/2 is transcriptionally active in differentiated adipocytes. However, USF-1/2 binding activity and PAI-1 transcription are not influenced by the 4 G/5 G-allele. These data possibly explain the observation that PAI-1 secretion from adipose tissue is not influenced by the PAI-1 promoter polymorphism.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Polymorphisme génétique
/
Facteurs de transcription
/
Régions promotrices (génétique)
/
Inhibiteur-1 d'activateur du plasminogène
/
Adipocytes
/
Protéines de liaison à l'ADN
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Mol Endocrinol
Sujet du journal:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Année:
2004
Type de document:
Article
Pays d'affiliation:
Allemagne