Ultraviolet B-induced LGI3 secretion protects human keratinocytes

Exp Dermatol. 2012 Sep;21(9):716-8. doi: 10.1111/j.1600-0625.2012.01550.x. Epub 2012 Jun 29.

Abstract

Leucine-rich glioma inactivated 3 (LGI3) is known to be expressed mainly in the brain. However, the expression and physiological roles of LGI3 in skin cells remain unknown. In this study, it was found for the first time that LGI3 is expressed mostly by normal human keratinocytes. Furthermore, ELISA analysis showed that HaCaT human keratinocytes increased LGI3 secretion after exposure to ultraviolet B (UVB) in a time- and dose-dependent manner. We next investigated the possible role of LGI3 in keratinocytes. LGI3 (50 ng/ml) increased survival of HaCaT cells by 20% after UVB irradiation (150 mJ/cm(2) ). It was also found that LGI3 stimulates the phosphorylation of Akt, which is involved in the cell survival-signalling cascade. Furthermore, LGI3 led to the phosphorylation of MDM2 and subsequent p53 degradation. Taken together, the data suggest that LGI3 may regulate p53 levels and that keratinocyte-derived LGI3 may act as a novel cytokine for skin homoeostasis.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / radiation effects
  • Nerve Tissue Proteins
  • Phosphorylation / drug effects
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Proteins / radiation effects
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / drug effects
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays

Substances

  • LGI3 protein, human
  • Nerve Tissue Proteins
  • Proteins
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins c-akt