FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription

Cell Death Differ. 2012 Apr;19(4):616-22. doi: 10.1038/cdd.2011.132. Epub 2011 Oct 14.

Abstract

PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia-associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, we have generated a transgenic mouse model expressing PAX3 driven by tyrosinase promoter in a tissue-specific fashion. These animals exhibit hyperpigmentation in the epidermis, evident in the skin color of their ears and tails. We showed that the darker skin color results from both increased melanocyte numbers and melanin synthesis. Together, our study delineated a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription. Moreover, our results suggest that this pathway might contribute to the regulation of melanocyte numbers and melanin levels, and thereby provide an alternative strategy to induce pigmentation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / physiology
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Humans
  • Melanocytes / cytology
  • Melanocytes / metabolism*
  • Mice
  • Mice, Transgenic
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / biosynthesis*
  • Paired Box Transcription Factors / genetics
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / physiology
  • Skin Pigmentation / physiology
  • Transcription, Genetic / physiology*
  • Transcriptional Activation / physiology*

Substances

  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Fibroblast Growth Factor 2
  • Pax3 protein, mouse