Interferon regulatory factor 6 is necessary, but not sufficient, for keratinocyte differentiation.
Interferon regulatory factor 6 is necessary, but not sufficient, for keratinocyte differentiation.
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DOI：
10.1038/jid.2011.272
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发表时间：
2012-01
影响因子：
6.5
通讯作者：
Dunnwald, Martine
中科院分区：
文献类型：
--
作者：
Biggs, Leah C.;Rhea, Lindsey;Schutte, Brian C.;Dunnwald, Martine
表皮增殖和分化的调节对于维持皮肤稳态是至关重要的。干扰素调节因子6（Irf 6）缺陷小鼠围产期死亡，表现出异位增殖和缺陷的表皮分化。我们试图确定这些表皮功能的破坏是否是细胞自主的，并使用胚胎Irf 6 −/−角质形成细胞来了解Irf 6在角质形成细胞增殖和分化中的特定作用。在缺乏Irf 6的情况下，角质形成细胞表现出异质性表型，存在大细胞。与野生型细胞相比，Irf 6 −/−角质形成细胞显示出更高的集落形成效率，表明Irf 6抑制长期增殖。Irf 6在培养的野生型角质形成细胞中以低水平存在，并且在体外诱导分化后上调，沿着早期分化标志物的上调。然而，Irf 6 −/−角质形成细胞不表达终末分化标志物。Irf 6在野生型角质形成细胞中的过表达不足以在生长条件下诱导分化标志物的表达。总之，这些结果表明Irf 6对于角质形成细胞分化是必要的，但还不足以。最后，使用转基因小鼠表达Lac-Z的调控下的增强子元件9.7kb上游的Irf 6的起始位点，我们证明了该元件有助于调节Irf 6在表皮和角质形成细胞培养。
Regulation of epidermal proliferation and differentiation is critical for maintenance of cutaneous homeostasis. Interferon Regulatory Factor 6 (Irf6) deficient mice die perinatally and exhibit ectopic proliferation and defective epidermal differentiation. We sought to determine if these disruptions of epidermal function were cell autonomous and used embryonic Irf6−/− keratinocytes to understand the specific role of Irf6 in keratinocyte proliferation and differentiation. In absence of Irf6, keratinocytes exhibited a heterogeneous phenotype with the presence of large cells. Irf6−/− keratinocytes displayed increased colony forming efficiency compared to wildtype cells, suggesting that Irf6 represses long-term proliferation. Irf6 was present at low levels in wildtype keratinocytes in culture and upregulated after induction of differentiation in vitro, along with upregulation of markers of early differentiation. However, Irf6−/− keratinocytes did not express markers of terminal differentiation. Overexpression of Irf6 in wildtype keratinocytes was insufficient to induce expression of markers of differentiation under growing conditions. Together, these results indicated that Irf6 is necessary, but not sufficient for keratinocyte differentiation. Finally, using a transgenic mouse expressing Lac-Z under the regulation of an enhancer element 9.7kb upstream of the Irf6 start site, we demonstrated that this element contributes to the regulation of Irf6 in the epidermis and keratinocytes in culture.
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影响因子：
7.8
作者：
Fisher, C;Jones, A;Roop, D R
通讯作者：
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影响因子：
3.5
作者：
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影响因子：
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作者：
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通讯作者：
Dixon, Michael J.
DOI：
10.1073/pnas.88.18.7948
发表时间：
1991-09-01
影响因子：
11.1
作者：
LEASK, A;BYRNE, C;FUCHS, E
通讯作者：
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