Functional analysis of ZFP36 proteins in keratinocytes.
Functional analysis of ZFP36 proteins in keratinocytes.
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DOI：
10.1016/j.ejcb.2016.04.007
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发表时间：
2016-08
影响因子：
6.6
通讯作者：
Frauke Prenzler;Annunziata Fragasso;A. Schmitt;B. Munz
中科院分区：
文献类型：
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作者：
Frauke Prenzler;Annunziata Fragasso;A. Schmitt;B. Munz
ZFP36家族的锌指蛋白，包括ZFP36、ZFP36L1和Zfp36L2，通过各自的mRNAs失稳来调节生长因子和细胞因子的产生。我们最近证实，在培养的角质形成细胞中，ZFP 36、ZFP 36L1和ZFP 36L2基因的表达是由生长因子和细胞因子诱导的，ZFP 36L1是角质形成细胞产生血管内皮生长因子的有效调节因子。我们进一步分析了ZFP 36蛋白在皮肤中的定位和功能，特别是在表皮角质形成细胞中。我们发现，在人的表皮细胞中，ZFP 36蛋白可以在基底层和基底层角质形成细胞中检测到，而ZFP 36L1和ZFP 36L2主要在基底层表达，这表明这三种蛋白在表皮中的表达是不同的和非多余的。同时，用特异性siRNA抑制ZFP 36或ZFP 36 L1的表达后，对其他基因的表达没有太大影响。此外，我们还发现ZFP 36和ZFP 36L1对角质形成细胞的周期、分化和凋亡都有不同程度的影响。最后，我们证明了与ZFP36L1类似，ZFP36是角质形成细胞产生血管内皮生长因子的有效调节因子。因此，这两种蛋白很可能是通过旁分泌机制来调节血管生成的。综上所述，我们的结果表明，ZFP36蛋白可能以一种多模式的方式控制皮肤的再上皮化和血管生成。
The ZFP36 family of zinc finger proteins, including ZFP36, ZFP36L1, and ZFP36L2, regulates the production of growth factors and cytokines via destabilization of the respective mRNAs. We could recently demonstrate that in cultured keratinocytes, expression of theZFP36,ZFP36L1, andZFP36L2genes is induced by growth factors and cytokines and that ZFP36L1 is a potent regulator of keratinocyte VEGF production.We now further analyzed the localization and function of ZFP36 proteins in the skin, specifically in epidermal keratinocytes.We found that in human epidermis, the ZFP36 protein could be detected in basal and suprabasal keratinocytes, whereasZFP36L1andZFP36L2were expressed mainly in the basal layer, indicating different and non-redundant functions of the three proteins in the epidermis.Consistently, upon inhibition ofZFP36orZFP36L1expression using specific siRNAs, there was no major effect on expression of the respective other gene. In addition, we demonstrate that both ZFP36 and ZFP36L1 influence keratinocyte cell cycle, differentiation, and apoptosis in a distinct manner. Finally, we show that similarly as ZFP36L1, ZFP36 is a potent regulator of keratinocyte VEGF production. Thus, it is likely that both proteins regulate angiogenesis via paracrine mechanisms.Taken together, our results suggest that ZFP36 proteins might control reepithelialization and angiogenesis in the skin in a multimodal manner.