| Autor: |
Iraburu MJ; Division of Gastroenterology, Hepatology, and Nutrition, Marion Bessin Liver Research Center, and Departments of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Domínguez-Rosales JA, Fontana L, Auster A, García-Trevijano ER, Covarrubias-Pinedo A, Rivas-Estilla AM, Greenwel P, Rojkind M |
| Jazyk: |
angličtina |
| Zdroj: |
Hepatology (Baltimore, Md.) [Hepatology] 2000 May; Vol. 31 (5), pp. 1086-93. |
| DOI: |
10.1053/he.2000.5981 |
| Abstrakt: |
Tumor necrosis factor alpha (TNF-alpha) is one of the key cytokines of the acute phase response and of many inflammatory processes. This cytokine has several antifibrogenic actions and down-regulates the expression of the type I collagen genes and induces the expression of metalloproteinases. Because TNF-alpha directly antagonizes some fibrogenic actions of transforming growth factor beta(1) (TGF-beta(1)), we considered it important to map the cis-acting regulatory element of the alpha1(I) collagen (col1a1) promoter involved in TNF-alpha responsiveness in hepatic stellate cells (HSC), to investigate the transcription factors that bind to it, and to establish possible mechanisms by which TNF-alpha down-regulates its expression. In this article, we show the presence of a functional TNF-alpha-responsive element (TaRE) in the -378 to -345 region of the col1a1 promoter. This element colocalizes with a previously reported TGF-beta(1)-responsive element. We further demonstrate that TNF-alpha induces nuclear translocation and binding of transcriptional complexes containing p20C/EBPbeta, p35C/EBPbeta, and C/EBPdelta to this sequence of the promoter. Transient overexpression of C/EBPdelta or p20C/EBPbeta, the natural dominant negative form of C/EBPbeta in HSC, down-regulated activity of a CAT reporter vector driven by -412 to +110 of the col1a1 promoter. Taken together, these data suggest that the -378 to -340 region of the col1a1 promoter is the site of convergence of different stimuli that ultimately modulate col1a1 gene transcription. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Plný text