Wnt Antagonist SFRP3 Inhibits the Differentiation of Mouse Hepatic Progenitor Cells
Wnt Antagonist SFRP3 Inhibits the Differentiation of Mouse Hepatic Progenitor Cells
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Wnt 拮抗剂 SFRP3 抑制小鼠肝祖细胞的分化
DOI：
10.1002/jcb.22254
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Tang, Ni
中科院分区：
文献类型：
--
作者：
Bi, Yang;Huang, Jiayi;Tang, Ni
Wnt/ β -连环蛋白通路在调控胚胎发育中起重要作用。肝细胞在发育过程中由内胚层分化而来。肝祖细胞（HPCs）已从胎儿肝脏和肝外组织中分离出来。目前大多数关于肝脏发育和肝分化的研究都集中在wnt、β -连环蛋白及其受体上。在这里，我们试图确定Writ拮抗剂在调节胎儿肝源性HPCs的肝分化中的作用。在胚胎期E12.5至出生后28天的小鼠肝组织中，我们发现19个Wnt基因中的13个和几乎所有的Writ受体/共受体在大多数阶段都有表达。然而，Writ拮抗剂SFRP2、SFRP3和Dkk2仅在早期被检测到。我们建立了可逆稳定的HPCs来源的E14.5小鼠前胎肝（HP14.5）并对其进行了表征。HP14.5细胞表达高水平的早期肝祖细胞标志物，但表达低水平或不表达晚期肝市场标志物。在地塞米松（Dex）刺激下，HP14.5细胞分化为成熟肝细胞。外源表达SFRP3可抑制dex诱导的FfP14.5细胞的晚期标志物表达和白蛋白启动子活性。此外，SFRP3显著抑制了dex诱导的pas阳性HP14.5细胞的糖原合成。因此，我们的研究结果表明，Wnt拮抗剂的表达随着肝分化的进展而减少，这表明平衡的Writ信号可能对小鼠肝脏发育和肝分化至关重要。j .细胞。中国生物医学工程学报，2009,31(2):393 - 393。(C) 2009 Wiley-Liss, Inc。
Wnt/beta-catenin pathway plays an important role in regulating embryonic development. Hepatocytes differentiate from endoderm during development. Hepatic progenitor cells (HPCs) have been isolated from fetal liver and extrahepatic tissues. Most current studies in liver development and hepatic differentiation have been focused on Wnts, beta-catenin, and their receptors. Here, we sought to determine the role of Writ antagonists in regulating hepatic differentiation of fetal liver-derived HPCs. Using mouse liver tissues derived from embryonic day E12.5 to postnatal day (PD) 28, we found that 13 of the 19 Wnt genes and almost all of Writ receptors/co-receptors were expressed in most stages. However, Writ antagonists SFRP2, SFRP3, and Dkk2 were only detected in the early stages. We established and characterized the reversible stable HPCs derived front E14.5 mouse fetal liver (HP14.5). HP14.5 cells were shown to express high levels of early liver progenitor cell markers, but low levels or none of late liver markets. HP14.5 cells were shown to differentiate into mature hepatocytes upon dexamethasone (Dex) stimulation. Dex-induced late marker expression and albumin promoter activity in FfP14.5 cells were inhibited by exogenous expression of SFRP3. Furthermore, Dex-induced glycogen synthesis of PAS-positive HP14.5 cells was significantly inhibited by SFRP3. Therefore, our results have demonstrated that the expression of Wnt antagonists decreases as hepatic differentiation progresses, suggesting that a balanced Writ signaling may be critical (hiring mouse liver development and hepatic differentiation. J. Cell. Biochem. 108: 295-303, 2009. (C) 2009 Wiley-Liss, Inc.