Sonic hedgehog stimulates mouse embryonic stem cell proliferation by cooperation of Ca2+/Protein kinase c and epidermal growth factor receptor as well as Gli1 activation

Sonic hedgehog stimulates mouse embryonic stem cell proliferation by cooperation of Ca2+/Protein kinase c and epidermal growth factor receptor as well as Gli1 activation
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DOI:
10.1634/stemcells.2007-0550
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发表时间:
2007-01-01
期刊:
影响因子:
5.2
通讯作者:
Han, Ho Jae
Han, Ho Jae
中科院分区:
医学2区
文献类型:
--
作者:
Heo, Jung Sun;Lee, Min Young;Han, Ho Jae

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Hedgehog信号传导在胚胎组织中干细胞生长的控制中具有重要作用。因此,本研究探讨了音刺猬(Shh)对小鼠胚胎干细胞自我更新的影响及其相关机制。Shh增加了被smoothened受体抑制所阻断的DNA合成。Shh需要Gli 1激活来诱导Notch/Hes-1和Wnt/β-连环蛋白的增加。Shh增加细胞内钙浓度([Ca 2 +](i))和蛋白激酶C(PKC)活性。我们发现Shh诱导的Gli 1 mRNA水平的增加需要[Ca 2 +] i和PKC。Shh增加了表皮生长因子受体(EGFR)的磷酸化,这是由基质金属蛋白酶抑制剂阻断。随后,委员会注意到,
Hedgehog signaling has an essential role in the control of stem cell growth in embryonic tissues. Therefore, this study examined the effect of sonic hedgehog (Shh) on the self-renewal of mouse embryonic stem (ES) cells and its related mechanisms. Shh increased DNA synthesis blocked by the inhibition of the smoothened receptor. Shh required Gli1 activation to induce the increases in Notch/Hes-1 and Wnt/beta-catenin. Shh increased the intracellular calcium concentration ([Ca2+](i)) and protein kinase C (PKC) activity. We show that the Shh-induced increase in the Gli1 mRNA level requires [Ca2+] i and PKC. Shh increased the phosphorylation of epidermal growth factor receptor ( EGFR), which is blocked by the matrix metalloproteinase inhibitor. Subsequently,