ZFP36L1 is regulated by growth factors and cytokines in keratinocytes and influences their VEGF production

ZFP36L1 is regulated by growth factors and cytokines in keratinocytes and influences their VEGF production
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DOI:
10.3109/08977190903578660
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发表时间:
2010-06-01
期刊:
影响因子:
1.8
通讯作者:
Munz, Barbara
Munz, Barbara
中科院分区:
生物学4区
文献类型:
--
作者:
Hacker, Christine;Valchanova, Ralitsa;Munz, Barbara

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角化细胞来源的生长因子和细胞因子在表皮稳态中起重要作用,特别是在皮肤伤口修复中。因此,我们分析了锌指蛋白ZFP36/ tristeprolin家族的潜在作用,锌指蛋白是这些因子的靶点,但也调节它们在角化细胞中的产生。我们发现ZFP36、ZFP36L1和ZFP36L2的表达可由多种生长因子和细胞因子以及抓伤诱导。由于ZFP36L1是血管内皮生长因子(VEGF) mRNA稳定性的调节剂,我们随后使用siRNA技术抑制ZFP36L1基因的表达。值得注意的是,在表皮生长因子刺激HaCaT角质形成细胞后,这种治疗导致这些细胞中VEGF水平的升高长期维持。综上所述,我们的研究结果表明ZFP36L1在伤口愈合中的重要作用。
Keratinocyte-derived growth factors and cytokines play an important role in epidermal homeostasis and particularly in cutaneous wound repair. Thus, we analyzed a potential role of the ZFP36/tristetraprolin family of zinc finger proteins, which are targets of these factors, but also regulate their production, in keratinocytes. We show that expression of ZFP36, ZFP36L1, and ZFP36L2 is induced by a broad variety of growth factors and cytokines, and by scratch wounding. Since ZFP36L1 is a modulator of vascular endothelium growth factor (VEGF) mRNA stability, we subsequently used siRNA technology to inhibit ZFP36L1 gene expression. Notably, this treatment resulted in prolonged maintenance of elevated VEGF levels in HaCaT keratinocytes upon epidermal growth factor stimulation of these cells. Taken together, our results suggest an important role of ZFP36L1 in wound healing.