Extracellular proteolysis alters tooth development in transgenic mice expressing urokinase-type plasminogen activator in the enamel organ
| Autor: | Hong-Ming Zhou, Anthony Nichols, Annelise Wohlwend, Isabelle Bolon, Jean-Dominique Vassalli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Gene Expression
Tooth/ embryology Mice Transgenic Dental Enamel Proteins/genetics Basement Membrane Metalloendopeptidases/ metabolism Mice Urokinase-Type Plasminogen Activator/genetics/ metabolism Dental Enamel Proteins stomatognathic system Transforming Growth Factor beta Ameloblasts Animals Dental Enamel Molecular Biology ddc:616 Amelogenin Metalloendopeptidases Dental Enamel/ embryology Urokinase-Type Plasminogen Activator Extracellular Matrix Up-Regulation Incisor stomatognathic diseases Tooth Transforming Growth Factor beta/metabolism Developmental Biology Extracellular Matrix/enzymology |
| Zdroj: | Development, Vol. 126, No 5 (1999) pp. 903-912 |
| ISSN: | 0950-1991 |
| Popis: | By catalyzing plasmin formation, the urokinase-type plasminogen activator (uPA) can generate widespread extracellular proteolysis and thereby play an important role in physiological and pathological processes. Dysregulated expression of uPA during organogenesis may be a cause of developmental defects. Targeted epithelial expression of a uPA-encoding transgene under the control of the keratin type-5 promoter resulted in enzyme production by the enamel epithelium, which does not normally express uPA, and altered tooth development. The incisors of transgenic mice were fragile, chalky-white and, by scanning electron microscopy, their labial surface appeared granular. This phenotype was attributed to a defect in enamel formation during incisor development, resulting from structural and functional alterations of the ameloblasts that differentiate from the labial enamel epithelium. Immunofluorescence revealed that disorganization of the ameloblast layer was associated with a loss of laminin-5, an extracellular matrix molecule mediating epithelial anchorage. Amelogenin, a key protein in enamel formation, was markedly decreased at the enamel-dentin junction in transgenics, presumably because of an apparent alteration in the polarity of its secretion. In addition, increased levels of active transforming growth factor-β could be demonstrated in mandibles of transgenic mice. Since the alterations detected could be attributed to uPA catalytic activity, this model provides evidence as to how dysregulated proteolysis, involving uPA or other extracellular proteases, may have developmental consequences such as those leading to enamel defects. |
| Databáze: | OpenAIRE |
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