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PMID: 15161662 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The American journal of pathology ·Vol. 164 ·No. 6 ·2004-06-00 ·Pages 2299-304

Bolon I, Zhou HM, Charron Y, Wohlwend A, Vassalli JD

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.

MeSH Terms
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
Chemicals
Plaur protein, mouse Receptors, Cell Surface Receptors, Urokinase Plasminogen Activator Plasminogen Urokinase-Type Plasminogen Activator
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bolon Isabelle
Department of Morphology, University of Geneva Medical School, Geneva, Switzerland.
Zhou Hong-Ming
Charron Yves
Wohlwend Annelise
Vassalli Jean-Dominique
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36 references, click to expand
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63786-8
Published
2004-06-00
Pages
2299-304
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1615761
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63786-8 PMC Full Text View journal details
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