title: Epidermal expression of neuropilin 1 protects murine keratinocytes from UVB-induced apoptosis.
abstract: BACKGROUND
  Neuropilin 1 (NRP1) is expressed on several cell types including neurons and endothelial cells, where it functions as an important regulator in development and during angiogenesis. As a cell surface receptor, NRP1 is able to bind to members of the VEGF family of growth factors and to secreted class 3 semaphorins. Neuropilin 1 is also highly expressed in keratinocytes, but the function of NRP1 in epidermal physiology and pathology is still unclear.
  
  
  RESULTS
  To elucidate the role of NRP1 in skin in vivo we generated an epidermis-specific neuropilin 1 knock out mouse model by using the Cre-LoxP-System. Mice were viable and fertile and did not display any obvious skin or hair defects. After challenge with UVB irradiation, we found that deletion of epidermal NRP1 leads to increased rates of apoptosis both in vitro and in vivo. NRP1-deficient primary keratinocytes cultured in vitro showed significantly higher rates of apoptosis 24 hours after UVB. Likewise, there is a significant increase of active caspase 3 positive cells in the epidermis of Keratin 14-Cre-NRP1 (-/-) mice 24 hours after UVB irradiation. By Western Blot analysis we could show that NRP1 influences the cytosolic levels of Bcl-2, a pro-survival member of the Bcl-2 family. After UVB irradiation the amounts of Bcl-2 decrease in both protein extracts from murine epidermis and in NRP1-deficient keratinocytes in vitro, whereas wild type cells retain their Bcl-2 levels. Likewise, levels of phospho-Erk and Rac1 were lower in NRP1-knock out keratinocytes, whereas levels of pro-apoptotic p53 were higher.
  
  
  CONCLUSIONS
  NRP1 expression in keratinocytes is dispensable for normal skin development. Upon UVB challenge, NRP1 contributes to the prevention of keratinocyte apoptosis. This pro-survival function of NRP1 is accompanied by the maintenance of high levels of the antiapoptotic regulator Bcl-2 and by lower levels of pro-apoptotic p53.
authors.affiliation: Department of Dermatology and Venerology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Riese
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Eilert
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Meyer
authors.forename: Meral
authors.initials: M
authors.lastname: Arin
authors.forename: Jens M
authors.initials: JM
authors.lastname: Baron
authors.forename: Sabine
authors.initials: S
authors.lastname: Eming
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.forename: Peter
authors.initials: P
authors.lastname: Kurschat
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism* / Q000528:radiation effects; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014466:Ultraviolet Rays; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D039942:Neuropilin-1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D020830:rac1 GTP-Binding Protein