Transient Expression of Ephrin B2 in Perinatal Skin Is Required for Maintenance of Keratinocyte Homeostasis
Transient Expression of Ephrin B2 in Perinatal Skin Is Required for Maintenance of Keratinocyte Homeostasis
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DOI：
10.1038/jid.2009.105
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发表时间：
2009-10-01
影响因子：
6.5
通讯作者：
Nishikawa, Shin-Ichi
中科院分区：
文献类型：
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作者：
Egawa, Gyohei;Osawa, Masatake;Nishikawa, Shin-Ichi
功能性皮肤的形成需要多个关键信号，这些信号在胚胎发生过程中反复涉及不同的过程。虽然Eph受体及其膜结合的ephrin配体在多种胚胎过程中发挥作用，但它们在皮肤发育中的功能尚未得到解决。在这里，我们发现ephrin B2在胚胎发育期间在毛芽中短暂表达，在围产期在真皮间充质细胞中短暂表达。角化细胞特异性ephrin B2靶向突变小鼠没有皮肤表型，而出生后全身消融ephrin B2导致角化细胞增殖增强。虽然同样的治疗会导致血管重构缺陷，但我们的分析表明，角化细胞表型不是由血管缺陷引起的缺氧引起的。有趣的是，我们发现IL-1家族分子的表达增强，这与角化细胞增殖的调节有关。基于这些观察结果，我们提出在围产期真皮间充质细胞中短暂表达ephrin B2在调节间充质微环境的活性中起作用，而间充质微环境调节角质形成细胞的增殖。
The formation of functional skin entails multiple key signals that are implicated repeatedly in distinct processes during embryogenesis. Although Eph receptors and their membrane-bound ephrin ligands play a role in a wide variety of embryonic processes, their function in skin development has not been addressed. Here, we show that ephrin B2 is transiently expressed in hair buds during embryogenesis and in dermal mesenchymal cells during the perinatal period. Keratinocyte-specific ephrin B2-targeted mutant mice exhibit no skin phenotype, whereas postnatal systemic ephrin B2 ablation results in the enhancement of keratinocyte proliferation. Although the same treatment results in a defect of vascular remodeling, our analyses showed that the keratinocyte phenotype is not caused by hypoxia due to vascular defects. Interestingly, we found an enhanced expression of IL-1 family molecules, which have been implicated in the regulation of keratinocyte proliferation. On the basis of these observations, we propose that the transient expression of ephrin B2 in perinatal dermal mesenchymal cells plays a role in adjusting the activity of the mesenchymal microenvironment that regulates proliferation of keratinocytes.