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Publication : Modulation of the plasminogen activator cascade during enhanced epidermal proliferation in vivo.

First Author  Jensen PJ Year  1996
Journal  Cell Growth Differ Volume  7
Issue  12 Pages  1793-804
PubMed ID  8959348 Mgi Jnum  J:39694
Mgi Id  MGI:87048 Citation  Jensen PJ, et al. (1996) Modulation of the plasminogen activator cascade during enhanced epidermal proliferation in vivo. Cell Growth Differ 7(12):1793-804
abstractText  Many lines of evidence support an involvement of urokinase plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) in the migration of a variety of cells, including normal keratinocytes and carcinoma lines. In the present study, uPA expression was found to be a characteristic not just of migratory but also of proliferative keratinocytes. A variety of naturally occurring and experimentally induced epidermal hyperproliferative conditions were examined in mice, including fetal and neonatal epidermis, tape-stripped epidermis, and epidermis from which the hairs had been gently plucked. In all cases, epidermal hyperproliferation was accompanied by elevated levels of uPA mRNA (as measured by in situ hybridization) and activity (as measured by zymography). uPA mRNA was predominantly localized in the basal and immediately suprabasal cells, which constitute the proliferative population. To determine whether a PAI was concomitantly elevated, in situ hybridization for PAI-1 and PAI-2 was performed. PAI-2 but not PAI-1 mRNA was detected in fetal and neonatal epidermis, localized in the spinous layers. Although mRNAs for both inhibitors were induced by tape-stripping or hair-plucking, their distribution was more focal and more transient than that of uPA mRNA. These findings show that uPA, but not its usual inhibitors, is consistently elevated in the proliferative population of keratinocytes in a diverse range of hyperproliferative states. Two hypotheses are suggested by these data: (a) uPA may play a regulatory role in the activation of epidermal proliferation; or (b) uPA may be involved in the vertical migration of keratinocytes that must accompany increased cell proliferation.
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