Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells

Biochem Biophys Res Commun. 2008 Dec 12;377(2):642-647. doi: 10.1016/j.bbrc.2008.10.049. Epub 2008 Oct 20.

Abstract

Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10mJ/cm(2)) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and it was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.

MeSH terms

  • CREB-Binding Protein / metabolism
  • Dose-Response Relationship, Radiation
  • Epidermal Cells
  • Epidermis / metabolism
  • Epidermis / radiation effects*
  • Humans
  • Imidazoles / pharmacology
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects*
  • MAP Kinase Kinase 4 / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / pharmacology
  • RNA, Small Interfering / genetics
  • Radiation Tolerance*
  • Thrombomodulin / biosynthesis*
  • Thrombomodulin / genetics
  • Ultraviolet Rays*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Imidazoles
  • Protein Kinase Inhibitors
  • Pyridines
  • RNA, Small Interfering
  • Thrombomodulin
  • CREB-Binding Protein
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • SB 203580