Identification of a glucocorticoid response element in the human transforming growth factor beta 1 gene promoter

• Published in: The international journal of biochemistry & cell biology Vol. 30; no. 5; pp. 623 - 627
• Main Authors: Parrelli, Jo M, Meisler, Natalie, Cutroneo, Kenneth R
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.1998
• Subjects: Animals; Cell Line; Fibrosis; Glucocorticoid response element; Glucocorticoids - metabolism; Glucocorticoids - pharmacology; Humans; Promoter Regions, Genetic; Rats; TGF-β1 gene; Transforming Growth Factor beta - genetics; Wound healing; FRS, fetal rat skin; Wound healing; GRE, glucocorticoid response element; Glucocorticoid response element; TGF-β1 gene; Fibrosis; TGF-β, transforming growth factor beta; GR, glucocorticoid receptor
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/S1357-2725(98)00005-3

TGF-β1, which has a stimulatory effect on dermal wound healing, has been implicated as the primary causative agent of fibrosis. Glucocorticoids such as dexamethasone normally inhibit wound healing and are capable of antagonizing the fibrotic effect of TGF-β1. Our data indicate the presence of a putative regulatory element responsive to glucocorticoids. Computer sequence analysis of the promoter region of the human TGF-β1 gene (Genbank Accession # J04431) revealed a consensus glucocorticoid response element, GRE (5′-AGAACA) located from (−1081) to (−1086) base pairs from the transcription start site. An oligonucleotide containing this site was obtained and labeled for use in gel mobility shift assays. The labeled oligonucleotide was found to bind both fetal rat skin nuclear extracts and purified recombinant glucocorticoid receptor. Unlabeled oligonucleotides containing a GRE from the rat procollagen type 1 promoter or a commercially supplied GRE competed effectively with the 32P-labeled GRE from the TGF-β1 promoter for binding to nuclear extracts. Addition of anti-glucocorticoid receptor revealed a supershifting of the labeled oligonucleotide-nuclear protein complex. These results indicate the presence of a putative GRE in the promoter region of the human TGF-β1 gene.