Induction of fibronectin mRNA by urokinase- and tissue-type plasminogen activator in human skin fibroblasts: differential role of u-PA and t-PA at the fibronectin protein level

Biological Chemistry
G De PetroSergio Barlati

Abstract

Plasminogen activators of the urokinase- and tissue-type and fetal calf serum (u-PA, t-PA, FCS) exert their mitogenic effect on quiescent human dermal fibroblasts and modulate the mRNA expression of cell-cycle related genes. The present study deals with the effects of PAs on the expression of fibronectin (FN), a heterodimeric extracellular matrix (ECM) protein that can be modulated in different ways by various mitogens. The kinetics of FN gene response was examined in quiescent fibroblasts upon PA stimulation (30 min -24 h). The results obtained evidenced that: (i) all mitogens tested (u-PA, t-PA and FCS) led to an increase of FN mRNA expression in early G1, as shown by the analysis of two sequences, III-9, common to all FN mRNAs, and EDA+, present only in the EDA+FN isoform; (ii) the kinetic profiles of FN mRNA stimulation were comparable for the three mitogens, although the effects on the FN-ECM assembly were distinct; (iii) t-PA and FCS led to FN assembly in the ECM, which was absent or decreased in u-PA-treated cultures. Immunobiochemical analysis of total FN and EDA+ FN showed that FN induced by t-PA was mainly dimeric (450-500 kDa), whereas FN induced by u-PA was mainly monomeric (230-250 kDa). These differences are proba...Continue Reading

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Citations

Jun 27, 2002·Seminars in Cancer Biology·J Labat-Robert
Jul 4, 2012·Biologie aujourd'hui·Jacqueline Labat-Robert
Jul 26, 2007·Archives of Environmental & Occupational Health·Liang-Che ChangHuang-Pin Wu

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