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

Abstract

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.

Acknowledgements

We thank Sabine Werner, ETH Zurich, for wound RNA.

Declaration of interest: Work in the authors' laboratory is supported by grants from the Deutsche Forschungsgemeinschaft (Mu 1556/3-1), the Sonnenfeld-Stiftung, Berlin, Germany, the Monika-Kutzner-Stiftung, Berlin Germany, and the Deutsche Stiftung für Herzforschung (DSHF). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.