Author:
Ratziu Vlad,Lalazar Avraham,Wong Linda,Dang Qi,Collins Colin,Shaulian Eitan,Jensen Susan,Friedman Scott L.
Abstract
Wound repair in the liver induces altered gene expression in stellate cells (resident mesenchymal cells) in a process known as “activation.” A zinc finger transcription factor cDNA,zf9, was cloned from rat stellate cells activatedin vivo. Zf9 expression and biosynthesis are increased markedly in activated cellsin vivocompared with cells from normal rats (“quiescent” cells). The factor is localized to the nucleus and the perinuclear zone in activated but not quiescent cells. Zf9 mRNA also is expressed widely in nonhepatic adult rat tissues and the fetal liver. Thezf9nucleotide sequence predicts a member of the Kruppel-like family with a unique N-terminal domain rich in serine–proline clusters and leucines. The humanzf9gene maps to chromosome 10P near the telomere. Zf9 binds specifically to a DNA oligonucleotide containing a GC box motif. The N-terminal domain of Zf9 (amino acids 1–201) is transactivating in the chimeric GAL4 hybrid system. InDrosophila schneidercells, full length Zf9 transactivates a reporter construct driven by the SV40 promoter/enhancer, which contains several GC boxes. A physiologic role for Zf9 is suggested by its transactivation of a collagen α1(I) promoter reporter. Transactivation of collagen α1(I) by Zf9 is context-dependent, occurring strongly in stellate cells, modestly in Hep G2 cells, and not at all inD. schneidercells. Our results suggest that Zf9 may be an important signal in hepatic stellate cell activation after liver injury.
Publisher
Proceedings of the National Academy of Sciences
Cited by
219 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献