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
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Giuseppina De Petro
Abstract
Plasminogen activators of the urokinase and tissuetype and fetal calf serum (uPA, tPA, FCS) exert their mitogenic effect on quiescent human dermal fibroblasts and modulate the mRNA expression of cellcycle 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 (uPA, tPA 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 FNECM assembly were distinct; (iii) tPA and FCS led to FN assembly in the ECM, which was absent or decreased in uPAtreated cultures. Immunobiochemical analysis of total FN and EDA + FN showed that FN induced by tPA was mainly dimeric (450 500 kDa), whereas FN induced by uPA was mainly monomeric (230 250 kDa). These differences are probably due to the differential enzymatic action of tPA and uPA on FN, which might be related to a differential role of the two PAs in several physiopathological conditions.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Non-Enzymatic Activities of Proteases: From Scepticism to Reality
- The Urokinase Plasminogen Activator Receptor in the Regulation of the Actin Cytoskeleton and Cell Motility
- The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
- Nervous System Pathology: The Fibrin Perspective
- Post-Transcriptional Regulation of Gene Expression in the Plasminogen Activation System
- Role of Myofibroblasts at the Invasion Front
- Transmodulation of Cell Surface Regulatory Molecules via Ectodomain Shedding
- The Plasminogen Activating System in Periodontal Health and Disease
- Apolipoprotein(a): Structure-Function Relationship at the Lysine-Binding Site and Plasminogen Activator Cleavage Site
- Anti-Invasive Effects of Green Tea Polyphenol EpiGalloCatechin-3-Gallate (EGCG), a Natural Inhibitor of Metallo and Serine Proteases
- Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions
- Activation of p38 MAP-Kinase and Caldesmon Phosphorylation Are Essential for Urokinase-Induced Human Smooth Muscle Cell Migration
- Growth Factor-Dependent Proliferation and Invasion of Muscle Satellite Cells Require the Cell-Associated Fibrinolytic System
- The Col-1 Module of Human Matrix Metalloproteinase-2 (MMP-2): Structural/Functional Relatedness between Gelatin-Binding Fibronectin Type II Modules and Lysine-Binding Kringle Domains
- Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands
- Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion
- The Role of Proteases in Fibronectin Matrix Remodeling in Thyroid Epithelial Cell Monolayer Cultures
- 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
- Platelet Activating Factor Inhibits the Expression of Matrix Metalloproteinases and Affects Invasiveness and Differentiation in a System of Human Neuroblastoma Clones
- UVA Light Stimulates the Production of Cathepsin G and Elastase-Like Enzymes by Dermal Fibroblasts: A Possible Contribution to the Remodeling of Elastotic Areas in Sun-Damaged Skin
- uPA-Silica-Particles (SP-uPA): A Novel Analytical System to Investigate uPA-uPAR Interaction and to Test Synthetic uPAR Antagonists as Potential Cancer Therapeutics
- Monocyte-Expressed Urokinase Regulates Human Vascular Smooth Muscle Cell Migration in a Coculture Model
- Distinct Expression Pattern of Two Related Human Proteins Containing Multiple Types of Protease-Inhibitory Modules
- Osteopontin Modulates Prostate Carcinoma Invasive Capacity through RGD-Dependent Upregulation of Plasminogen Activators
- Expression of Matrix Metalloproteases (MMP-2, MT1-MMP) and Their Tissue Inhibitor (TIMP-2) by Rat Sertoli Cells in Culture: Implications for Spermatogenesis