Functional Characterization of Human ZF9 promoter region

Abstract

Zf9/core promoter-binding protein, a Kruppel-like zinc finger transcription factor is induced early in hepatic stellate cell (HSC) activation and transactivates TGF- 1 and TGF- receptors, types I and II in response to fibrogenic stimuli. To understand the role of Zf9 as the regulator of liver cirrhosis, we cloned 3kb sized zf9 promoter from human genomic DNA and generated 11 kinds of zf9 reporter constructs which were 3kb, 2.4kb, 2.2kb, 1.8kb, 1.6kb, 1.5kb, 1.1kb, 1.0kb, 0.9kb, 0.8kb, 0.5kb-sized respectively. Zf9 promoter was inhibited by TGF- 1 or SP1 in Hep3B or SK-Hep1, the human liver cancer cells. When PGF2 was treated as the fibrogenic stimulus, zf9 promoter was activated in HSC-T6 cells (an SV40-immortalized rat HSC line). Also, zf9 promoter was characterized in LX2, the human hepatic stellate cell which was pretreated by EGCG before PGF2a treatement to investigate the preventive effect of EGCG for liver cirrhosis.