Back
Full-text
Journal article

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

  • 2004-05-27
Published in:
  • The American journal of pathology. - 2004
Animals
Crosses, Genetic
Dental Enamel
Dental Enamel Hypoplasia
Gene Expression Regulation
Incisor
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Phenotype
Plasminogen
Receptors, Cell Surface
Receptors, Urokinase Plasminogen Activator
Tooth Abnormalities
Urokinase-Type Plasminogen Activator
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/5386
Statistics
Document views: 28 File downloads:
  • Full-text: 0