Grhl2 regulation of SPINT1 expression controls salivary gland development.
Grhl2 regulation of SPINT1 expression controls salivary gland development.
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Grhl2 对 SPINT1 表达的调节控制着唾液腺的发育。
DOI：
10.1016/j.bbrc.2018.08.166
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Sakai T
中科院分区：
文献类型：
--
作者：
Matsushita T;Sakai M;Yoshida H;Morita S;Hieda Y;Sakai T
唾液腺的发育以广泛的分支形态发生和管腔形成为特征，后者与腺泡和导管细胞的分化密切相关。尽管包括信号传导和细胞粘附分子在内的各种分子都与唾液腺发育有关，但调节这些分子表达和腺体形态发育的转录因子（TF）在很大程度上尚不清楚。在这里，我们表明，敲低上皮TF，Grainyhead样2（Grhl 2），与siRNA在发育中的小鼠下颌下腺（SMG）体外培养导致上皮发育迟缓。这种延迟是伴随着抑制细胞粘附分子，如E-钙粘蛋白和细胞外蛋白酶抑制剂SPINT 1的基因表达，并与基底层蛋白层粘连蛋白的无序沉积。ChIP-PCR结果显示Grhl 2蛋白与SMG中的Spint 1基因结合。值得注意的是，在培养的SMG中添加重组SPINT 1蛋白克服了Grhl 2 siRNA对上皮发育和层粘连蛋白沉积的抑制作用。这些发现表明，SPINT 1表达的Grhl 2调节控制唾液腺发育。
Development of the salivary gland is characterized by extensive branching morphogenesis and lumen formation, the latter of which is closely associated with differentiation into acinar and ductal cells. Although various molecules, including signaling and cell adhesion molecules, have been implicated in salivary gland development, transcription factors (TFs) regulating the expression of those molecules and morphological development of the gland are largely unknown. Here we show that knockdown of the epithelial TF, Grainyhead-like 2 (Grhl2), with siRNA in developing mouse submandibular salivary gland (SMG) culturedex vivoresulted in retardation of epithelial development. This retardation was concomitant with suppression of gene expression for the cell adhesion molecules, such as E-cadherin and the extracellular protease inhibitor SPINT1, and with the disorganized deposition of the basal lamina protein laminin. ChIP-PCR demonstrated the binding of Grhl2 protein to theSpint1gene in the SMG. Notably, addition of recombinant SPINT1 protein in cultured SMG overcame the suppressive effects of Grhl2 siRNA on epithelial development and laminin deposition. These findings show that Grhl2 regulation of SPINT1 expression controls salivary gland development.
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影响因子：
4.6
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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影响因子：
3.2
作者：
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通讯作者：
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小鼠胚胎颌下腺上皮形态发生：其与上皮和间质组织的关系
DOI：
--
发表时间：
1997
期刊：
Development, Growth and Differentiation
影响因子：
--
作者：
Y. Hieda;Y. Nakanishi
通讯作者：
Y. Nakanishi