en
Scientific article
English

Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis

Published inEMBO journal, vol. 19, no. 17, p. 4817-4826
Publication date2000
Abstract

Urokinase-type plasminogen activator (uPA) is a potent catalyst of extracellular proteolysis, which also binds to a high-affinity plasma membrane receptor (uPAR). Binding of uPA may influence pericellular proteolysis and/or activate intracellular signal transduction. Transgenic mice overexpressing either uPA or uPAR in basal epidermis and hair follicles had no detectable cutaneous alterations. In contrast, bi-transgenic mice overexpressing both uPA and uPAR, obtained by crossing the two transgenic lines, developed extensive alopecia induced by involution of hair follicles, epidermal thickening and sub-epidermal blisters. The phenotype was due to uPA catalytic activity since combined overexpression of uPAR and uPAR-binding but catalytically inactive uPA in the same tissue was not detrimental in another bi-transgenic line. It was accompanied by increased plasmin-generating capacity, up-regulation and activation of matrix metalloproteinases type-2 and -9, and cleavage of uPAR. Thus, combined overexpression of uPA and uPAR acts in synergy to promote pathogenic extracellular proteolysis.

Keywords
  • Animals
  • Base Sequence
  • Catalysis
  • Cells, Cultured
  • DNA Primers
  • Hydrolysis
  • Keratinocytes/cytology/enzymology/metabolism
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Receptors, Cell Surface/genetics/metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Transgenes
  • Urokinase-Type Plasminogen Activator/genetics/metabolism
Citation (ISO format)
ZHOU, Hong-Ming et al. Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis. In: EMBO journal, 2000, vol. 19, n° 17, p. 4817–4826. doi: 10.1093/emboj/19.17.4817
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Article (Accepted version)
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Identifiers
ISSN of the journal0261-4189
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