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Transforming growth factor beta-1 stimulates invasivity of hepatic stellate cells by engagement of the cell-associated fibrinolytic system.
Growth Factors. 2001; 19(2):87-100.GF

Abstract

The activation of hepatic stellate cells (HSC) during liver fibrogenesis has been shown to be mediated by paracrine and autocrine loops involving transforming growth factor-beta1 (TGF-beta1) as the main fibrogenic mediator secreted by activated macrophages, endothelial cells and liberated by disintegrated platelets. The cell-associated plasminogen activation system regulates extracellular matrix (ECM) catabolism and cell movement. We have studied whether TGF-beta1 could modulate the plasminogen activation system in human HSC and the role of such protease system in the activity of TGF-beta1 on HSC. Urokinase plasminogen activator receptors (u-PAR), u-PA and plasminogen activator inhibitor type 1 (PAI-1) were determined by immunoassay and RNase protection assay. Cell migration, evaluated either as chemotaxis or as chemoinvasion, was studied in Boyden chambers after addition of TGF-beta1, and inhibition with anti-u-PA and anti-u-PAR antagonists [antibodies against u-PA and u-PAR and antisense oligonucleotides (aODN) against u-PAR mRNA]. We have shown that TGF-beta1 is not mitogenic for HSC, while it is a powerful motogen either in chemotaxis or chemoinvasion assays. TGF-beta1 up-regulates the synthesis and expression of PAI-1, as well as u-PAR expression and exposure at the cell membrane, while it does not affect u-PA levels. TGF-beta1-dependent chemoinvasion of reconstituted basement membrane exploits the cell-associated plasminogen activation system, since it is blocked by monoclonal antibodies against u-PA and against various u-PAR domains, as well as by anti-u-PAR aODN. We have also observed a cumulative effect of TGF-beta1, b-FGF and PDGF in the invasion assay of HSC: in the presence of low amounts of TGF-beta1 the chemoinvasive activity of PDGF and bFGF is dramatically increased. Also this cooperation requires u-PAR and is inhibited by monoclonal antibodies against u-PAR domains I, II and III.

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Authors+Show Affiliations

Fibbi G
Department of Experimental Pathology and Oncology, University of Florence, Italy.
Pucci M
No affiliation info available
D'Alessio S
No affiliation info available
Grappone C
No affiliation info available
Pellegrini G
No affiliation info available
Salzano R
No affiliation info available
Casini A
No affiliation info available
Milani S
No affiliation info available
Del Rosso M
No affiliation info available

MeSH

AnimalsCell DivisionCell MovementCells, CulturedCollagenDose-Response Relationship, DrugDrug CombinationsEnzyme-Linked Immunosorbent AssayFibrinolysisFibroblast Growth Factor 2HumansLamininLiverMacrophagesMiceNeoplasm InvasivenessOligonucleotides, AntisensePlatelet-Derived Growth FactorProtein Structure, TertiaryProteoglycansReceptors, Cell SurfaceReceptors, Urokinase Plasminogen ActivatorRibonucleasesTime FactorsTransforming Growth Factor betaTransforming Growth Factor beta1Wound Healing

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11769974

Citation

Fibbi, G, et al. "Transforming Growth Factor Beta-1 Stimulates Invasivity of Hepatic Stellate Cells By Engagement of the Cell-associated Fibrinolytic System." Growth Factors (Chur, Switzerland), vol. 19, no. 2, 2001, pp. 87-100.
Fibbi G, Pucci M, D'Alessio S, et al. Transforming growth factor beta-1 stimulates invasivity of hepatic stellate cells by engagement of the cell-associated fibrinolytic system. Growth Factors. 2001;19(2):87-100.
Fibbi, G., Pucci, M., D'Alessio, S., Grappone, C., Pellegrini, G., Salzano, R., Casini, A., Milani, S., & Del Rosso, M. (2001). Transforming growth factor beta-1 stimulates invasivity of hepatic stellate cells by engagement of the cell-associated fibrinolytic system. Growth Factors (Chur, Switzerland), 19(2), 87-100.
Fibbi G, et al. Transforming Growth Factor Beta-1 Stimulates Invasivity of Hepatic Stellate Cells By Engagement of the Cell-associated Fibrinolytic System. Growth Factors. 2001;19(2):87-100. PubMed PMID: 11769974.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transforming growth factor beta-1 stimulates invasivity of hepatic stellate cells by engagement of the cell-associated fibrinolytic system. AU - Fibbi,G, AU - Pucci,M, AU - D'Alessio,S, AU - Grappone,C, AU - Pellegrini,G, AU - Salzano,R, AU - Casini,A, AU - Milani,S, AU - Del Rosso,M, PY - 2002/1/5/pubmed PY - 2002/5/29/medline PY - 2002/1/5/entrez SP - 87 EP - 100 JF - Growth factors (Chur, Switzerland) JO - Growth Factors VL - 19 IS - 2 N2 - The activation of hepatic stellate cells (HSC) during liver fibrogenesis has been shown to be mediated by paracrine and autocrine loops involving transforming growth factor-beta1 (TGF-beta1) as the main fibrogenic mediator secreted by activated macrophages, endothelial cells and liberated by disintegrated platelets. The cell-associated plasminogen activation system regulates extracellular matrix (ECM) catabolism and cell movement. We have studied whether TGF-beta1 could modulate the plasminogen activation system in human HSC and the role of such protease system in the activity of TGF-beta1 on HSC. Urokinase plasminogen activator receptors (u-PAR), u-PA and plasminogen activator inhibitor type 1 (PAI-1) were determined by immunoassay and RNase protection assay. Cell migration, evaluated either as chemotaxis or as chemoinvasion, was studied in Boyden chambers after addition of TGF-beta1, and inhibition with anti-u-PA and anti-u-PAR antagonists [antibodies against u-PA and u-PAR and antisense oligonucleotides (aODN) against u-PAR mRNA]. We have shown that TGF-beta1 is not mitogenic for HSC, while it is a powerful motogen either in chemotaxis or chemoinvasion assays. TGF-beta1 up-regulates the synthesis and expression of PAI-1, as well as u-PAR expression and exposure at the cell membrane, while it does not affect u-PA levels. TGF-beta1-dependent chemoinvasion of reconstituted basement membrane exploits the cell-associated plasminogen activation system, since it is blocked by monoclonal antibodies against u-PA and against various u-PAR domains, as well as by anti-u-PAR aODN. We have also observed a cumulative effect of TGF-beta1, b-FGF and PDGF in the invasion assay of HSC: in the presence of low amounts of TGF-beta1 the chemoinvasive activity of PDGF and bFGF is dramatically increased. Also this cooperation requires u-PAR and is inhibited by monoclonal antibodies against u-PAR domains I, II and III. SN - 0897-7194 UR - https://www.unboundmedicine.com/medline/citation/11769974/Transforming_growth_factor_beta_1_stimulates_invasivity_of_hepatic_stellate_cells_by_engagement_of_the_cell_associated_fibrinolytic_system_ L2 - https://www.tandfonline.com/doi/full/10.3109/08977190109001078 DB - PRIME DP - Unbound Medicine ER -