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

Zhou, Hong-Ming
Published in American Journal of Pathology. 2004, vol. 164, no. 6, p. 2299-304
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 AnimalsCrosses, GeneticDental Enamel/pathologyDental Enamel Hypoplasia/genetics/pathologyGene Expression Regulation/drug effectsIncisor/pathologyMiceMice, Inbred C57BLMice, Inbred CBAMice, TransgenicPhenotypePlasminogen/deficiency/genetics/physiologyReceptors, Cell Surface/genetics/metabolismReceptors, Urokinase Plasminogen ActivatorTooth Abnormalities/genetics/pathologyUrokinase-Type Plasminogen Activator/drug effects/genetics
PMID: 15161662
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BOLON, Isabelle et al. Plasminogen mediates the pathological effects of urokinase-type plasminogen activator overexpression. In: American Journal of Pathology, 2004, vol. 164, n° 6, p. 2299-304. https://archive-ouverte.unige.ch/unige:3904

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Deposited on : 2009-10-23

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