Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis
Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis
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DOI：
10.1073/pnas.95.16.9500
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Friedman, SL
中科院分区：
文献类型：
--
作者：
Ratziu, V;Lalazar, A;Friedman, SL
肝脏创伤修复诱导星状细胞(常驻间充质细胞)的基因表达发生变化，这一过程被称为“激活”。从活体激活的大鼠星状细胞中克隆了锌指转录因子基因ZF9。与正常大鼠细胞(“静止”细胞)相比，体内激活细胞ZF9的表达和生物合成显著增加，该因子定位于激活细胞的核和核周，而不是静止细胞。ZF9基因在非肝性成年大鼠组织和胎肝中也广泛表达。ZF9核苷酸序列预测了Kruppel样家族的一个成员，该家族具有一个独特的N-末端结构域，富含丝氨酸-脯氨酸簇和亮氨酸。人类ZF9基因定位于端粒附近的POP染色体。ZF9与含有GC盒基序的DNA寡核苷酸特异性结合，ZF9的N-末端结构域(氨基酸1-201)在嵌合GAL4杂交系统中反式激活。在果蝇施耐德细胞中，全长ZF9反式激活由SV40启动子/增强子驱动的报告结构，该结构包含几个GC盒。ZF9对胶原α1(I)启动子的反式激活是一种生理作用。ZF9对胶原α1(I)的反式激活是上下文依赖的，在星状细胞中强烈发生，在Hep G2细胞中少量发生，在D.Schneider细胞中几乎不发生。我们的结果表明，ZF9可能是肝损伤后肝星状细胞激活的重要信号。
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 activated in vivo. Zf9 expression and biosynthesis are increased markedly in activated cells in vivo compared 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. The zf9 nucleotide sequence predicts a member of the Kruppel-like family with a unique N-terminal domain rich in serine-proline clusters and leucines. The human Zf9 gene maps to chromosome POP 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. In Drosophila schneider cells, 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 alpha 1 (I) promoter reporter, Transactivation of collagen alpha 1 (I) by Zf9 is context-dependent, occurring strongly in stellate cells, modestly in Hep G2 cells, and not at all in D. schneider cells, Our results suggest that Zf9 may be an important signal ire hepatic stellate cell activation after liver injury.