Microarray analysis of UVB-regulated genes in keratinocytes: downregulation of angiogenesis inhibitor thrombospondin-1

J Dermatol Sci. 2004 May;34(3):185-94. doi: 10.1016/j.jdermsci.2004.01.004.

Abstract

Background: Ultraviolet (UV) B light is an environmental mutagen that induces changes in cutaneous gene expression leading to immune suppression and carcinogenesis. Keratinocytes are a primary target for UVB.

Objective: To further delineate UVB-induced gene expression changes in keratinocytes.

Methods: cDNA microarray technology was utilized to examine gene expression in normal human KC (NHKC) following 20 mJcm(-2) UVB irradiation. Data was confirmed by semi-quantitative RT-PCR.

Results: Microarray analysis revealed 57 genes were upregulated, and 27 genes were downregulated, by at least two-fold following UVB. One downregulated gene was the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1). Semi-quantitative RT-PCR confirmed persistent downregulation of TSP-1 up to 18h following UVB. Microarray analysis also revealed upregulation of platelet-derived endothelial cell growth factor (PD-ECGF)--an angiogenesis activator.

Conclusion: Our results suggest a gene expression mechanism by which UVB induces an angiogenic switch in keratinocytes. This may represent an important early event promoting neovascularization and growth of cutaneous neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Down-Regulation / radiation effects
  • Gene Expression / radiation effects
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / physiology*
  • Keratinocytes / radiation effects*
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / physiopathology
  • Oligonucleotide Array Sequence Analysis
  • Skin Neoplasms / etiology
  • Skin Neoplasms / physiopathology
  • Thrombospondin 1 / genetics*
  • Ultraviolet Rays / adverse effects*

Substances

  • Thrombospondin 1