en
Scientific article
English

Plasminogen mediates the pathological effects of urokinase-type plasminogen activator overexpression

Published inThe American journal of pathology, vol. 164, no. 6, p. 2299-2304
Publication date2004
Abstract

Increased expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is associated with different pathological conditions. Both uPAR-mediated signaling and plasmin-catalyzed extracellular proteolysis may contribute to pathogenesis. To evaluate the involvement of plasminogen in such circumstances, we have taken advantage of transgenic mouse models in which overexpression of uPA and/or uPAR in enamel epithelium, basal epidermis, and hair follicles leads to a pathological phenotype; uPA transgenic mice have chalky-white incisors and, when uPAR is co-expressed, develop extensive alopecia, epidermal thickening, and subepidermal blisters. We report here that when these transgenic mice were backcrossed into a plasminogen-deficient (Plg-/-) background, the dental and skin phenotypes appeared completely normal. Heterozygous Plg+/- transgenic mice exhibited a haplo-insufficiency, with an intermediate or normal phenotype. These results do not argue in favor of a role for uPAR-mediated signaling in our experimental model; rather, they demonstrate an essential, dose-dependent, requirement for plasminogen in uPA-mediated tissue alterations. They also support the hypothesis that plasminogen could play a part in certain skin diseases.

Keywords
  • Animals
  • Crosses, Genetic
  • Dental Enamel/pathology
  • Dental Enamel Hypoplasia/genetics/pathology
  • Gene Expression Regulation/drug effects
  • Incisor/pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Phenotype
  • Plasminogen/deficiency/genetics/physiology
  • Receptors, Cell Surface/genetics/metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Tooth Abnormalities/genetics/pathology
  • Urokinase-Type Plasminogen Activator/drug effects/genetics
Citation (ISO format)
BOLON, Isabelle et al. Plasminogen mediates the pathological effects of urokinase-type plasminogen activator overexpression. In: The American journal of pathology, 2004, vol. 164, n° 6, p. 2299–2304.
Main files (1)
Article (Accepted version)
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Identifiers
ISSN of the journal0002-9440
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