אסיף מאגר המחקר החקלאי

Transcriptional activation of transforming growth factor β1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1: Potential mechanisms for autocrine fibrogenesis in response to injury

Year:

1998

Source of publication :

Authors :

Volume :

273

Co-Authors:

Kim, Y., Lab. of Cell Reg. and Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892, United States
Ratziu, V., Depts. of Med. and Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, United States, Serv. d'Hepatogastroenterologie G., 47-83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France
Choi, S.-G., Lab. of Cell Reg. and Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892, United States
Lalazar, A., Depts. of Med. and Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, United States, Volcani Agric. Res. Org. Institute, Bet Dagan 50250, Israel
Theiss, G., Bayer A.G., D-42096 Wuppertal, Germany
Dang, Q., Depts. of Med. and Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, United States, Systemix Inc., 3155 Porter Ave., Palo Alto, CA 94304, United States
Kim, S.-J., Lab. of Cell Reg. and Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892, United States
Friedman, S.L., Depts. of Med. and Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, United States, Box 1123, Mount Sinai School of Medicine, 1425 Madison Ave., New York, NY 10029-6574, United States

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Abstract:

We have explored the regulation of transforming growth factor β (TGF- β) activity in tissue repair by examining the interactions of Zf9/core promoter-binding protein, a Kruppel-like zinc finger transcription factor induced early in hepatic stellate cell (HSC) activation, with promoters for TGF-β1 and TGF-β receptors, types I and II. Nuclear extracts from culture- activated HSCs bound avidly by electrophoretic mobility shift assay to two tandem GC boxes within the TGF-β1 promoter but minimally to a single GC box; these results correlated with transactivation by Zf9 of TGF-β1 promoter- reporters. Zf9 transactivated the full-length TGF-β1 promoter in either primary HSCs, HSC-T6 cells (an SV40-immortalized rat HSC line), Hep G2 cells, or Drosophila Schneider (S2) cells. Recombinant Zf9-GST also bound to GC box sequences within the promoters for the types I and II TGF-β receptors. Both type I and type II TGF-β receptor promoters were also transactivated by Zf9 in mammalian cells but not in S2 cells. In contrast, Sp1 significantly transactivated both receptor promoters in S2 cells. These results suggest that (a) Zf9/core promoter-binding protein may enhance TGF-β activity through transactivation of both the TGF-β1 gene and its key signaling receptors, and (b) transactivating potential of Zf9 and Sp1 toward promoters for TGF-β1 and its receptors are not identical and depend on the cellular context.

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