Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells
Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells
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DOI：
10.1016/j.bbrc.2007.12.085
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发表时间：
2008-02-29
影响因子：
3.1
通讯作者：
Haeussinger, Dieter
中科院分区：
文献类型：
--
作者：
Kordes, Claus;Sawitza, Iris;Haeussinger, Dieter
众所周知，肝星状细胞（HSC）发育为细胞，被认为有助于肝纤维化。最近的数据表明，HSC是具有分化为内皮细胞和肝细胞谱系的细胞的能力的祖细胞。目前的研究表明，β-连环蛋白依赖的经典Wnt信号在新鲜分离的大鼠HSC中是活跃的。通过糖原合成酶激酶3 β抑制剂TWS 119模拟培养的HSC中的经典Wnt途径，导致β-连环蛋白磷酸化减少，诱导β-连环蛋白核转位，谷氨酰胺合成酶产生增加，阻碍α-平滑肌肌动蛋白和Wnt 5a的合成，但促进胶质细胞酸性蛋白Writ I Ob和配对样同源结构域转录因子2c的表达。此外，经典Writ信号降低DNA合成，阻碍HSC进入细胞周期。研究结果表明，β-连环蛋白依赖的Writ信号维持HSC的静止状态，并且与干细胞和祖细胞类似，影响它们的发育命运。(C)2007年爱思唯尔公司All rights reserved.
It is well known that hepatic stellate cells (HSC) develop into cells, which are thought to contribute to liver fibrogenesis. Recent data suggest that HSC are progenitor cells with the capacity to differentiate into cells of endothelial and hepatocyte lineages. The present study shows that beta-catenin-dependent canonical Wnt signaling is active in freshly isolated HSC of rats. Mimicking of the canonical Wnt pathway in cultured HSC by TWS119, an inhibitor of the glycogen synthase kinase 3 beta, led to reduced beta-catenin phosphorylation, induced nuclear translocation of beta-catenin, elevated glutamine synthetase production, impeded synthesis of alpha-smooth muscle actin and Wnt5a, but promoted the expression of glial fibrillary acidic protein, Writ I Ob, and paired-like homeodomain transcription factor 2c. In addition, canonical Writ signaling lowered DNA synthesis and hindered HSC from entering the cell cycle. The findings demonstrate that beta-catenin-dependent Writ signaling maintains the quiescent state of HSC and, similar to stem and progenitor cells, influences their developmental fate. (C) 2007 Elsevier Inc. All rights reserved.