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

Growth Factors. 2010 Jun;28(3):178-90. doi: 10.3109/08977190903578660.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyrate Response Factor 1 / genetics
  • Butyrate Response Factor 1 / physiology*
  • Cells, Cultured
  • Cytokines / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Keratinocytes / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Tristetraprolin / genetics
  • Tristetraprolin / physiology*
  • Vascular Endothelial Growth Factors / genetics
  • Vascular Endothelial Growth Factors / metabolism*
  • Wound Healing*

Substances

  • Butyrate Response Factor 1
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Transcription Factors
  • Tristetraprolin
  • Vascular Endothelial Growth Factors
  • ZFP36 protein, human
  • ZFP36L1 protein, human
  • ZFP36L2 protein, human