Schnabl, Bernd and Hu, Kanghong and Muhlbauer, Marcus and Hellerbrand, Claus and Stefanovic, Branko and Brenner, David A. and Schoelmerich, Juergen (2005) Zinc finger protein 267 is up-regulated during the;activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 335 (1). pp. 87-96. ISSN 0006-291X, 1090-2104
Full text not available from this repository. (Request a copy)Abstract
Activation of hepatic stellate cells (HSCs) is the central event in the development of liver fibrosis and cirrhosis. The transdifferentiation process of quiescent into activated HSCs requires a complete reprogramming in gene expression, which is governed by modulation of transcriptional activators or repressors. Using microarray analysis to identify genes differentially expressed during the activation process of human HSCs, zinc finger protein 267 (ZNF267) mRNA was up-regulated in activated HSCs and in cirrhotic human liver. ZNF267 belongs to the family of Kruppel-like zinc fingers and contains a conserved KRAB (Kruppel associated box) A and B domain in the N-terminal part outside the C-terminal region of zinc fingers. ZNF267constructs containing enhanced cyan fluorescence protein were constitutively localized in the nucleus. When fused to GAL4-DNA binding domain, full-length ZNF267 and all constructs encompassing KRAB A domain showed transcriptional repressor activity. Microarray analysis and RNase protection assays showed that ZNF267 represses MMP-10 gene expression, which was confirmed by reporter gene assays. Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10 might promote liver fibrogenesis through alteration of matrix degradation in vivo. (c) 2005 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; MATRIX METALLOPROTEINASES; HYDROGEN-PEROXIDE; REPRESSOR DOMAIN; EXPRESSION; RAT; KRAB; COLLAGEN; LIVER; INHIBITORS; Kruppel-like zinc finger proteins; Kruppel associated box; transcriptional repressor; liver fibrosis; collagen |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Apr 2021 07:43 |
| Last Modified: | 27 Apr 2021 07:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35623 |
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