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Functions of the fibrinolytic system in human Ito cells and its control by basic fibroblast and platelet-derived growth factor.
Hepatology. 1999 Mar; 29(3):868-78.Hep

Abstract

During liver fibrogenesis, hepatic stellate cells (HSC) proliferate and migrate under the influence of growth factors, including platelet-derived growth factor (PDGF) and basic-fibroblast growth factor (b-FGF). The plasminogen activation system regulates extracellular matrix (ECM) catabolism and cell movement. We evaluated the expression and biological functions of the plasminogen activation system in human HSC and its interaction with PDGF and b-FGF. Urokinase-plasminogen activator receptors (u-PAR) were measured by radioligand binding, cell cross-linking, immunoassay, and RNAse protection assay. u-PA and plasminogen activator inhibitors (PAIs) expression and activities were analyzed by zymography, immunoassay, and RNase protection assay. Cell migration and proliferation, studied in Boyden chambers and by microscopic counting, were evaluated after the addition of PDGF, b-FGF, and blockade with anti-u-PA, anti-u-PAR antibodies, and antisense oligodeoxynucleotides (aODN) against u-PAR mRNA. We have shown that HSC produce u-PAR, u-PA, and PAI-1. PDGF and b-FGF up-regulate u-PA and u-PAR, but not PAI-1, and exogenous addition of u-PA stimulates HSC proliferation, chemotaxis, and chemoinvasion. Inhibition of u-PA/u-PAR with antibodies against u-PA or u-PAR and with u-PAR aODN inhibit the proliferative, chemotactic, and chemoinvasive activity of PDGF and b-FGF. These findings indicate that u-PA and u-PAR are required for the mitogenic and chemoinvasive activity of PDGF and b-FGF on HSC.

Authors+Show Affiliations

Institute of General Pathology, Department of Clinical Pathophysiology, University of Florence, Florence, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10051491

Citation

Fibbi, G, et al. "Functions of the Fibrinolytic System in Human Ito Cells and Its Control By Basic Fibroblast and Platelet-derived Growth Factor." Hepatology (Baltimore, Md.), vol. 29, no. 3, 1999, pp. 868-78.
Fibbi G, Pucci M, Grappone C, et al. Functions of the fibrinolytic system in human Ito cells and its control by basic fibroblast and platelet-derived growth factor. Hepatology. 1999;29(3):868-78.
Fibbi, G., Pucci, M., Grappone, C., Pellegrini, G., Salzano, R., Casini, A., Milani, S., & Del Rosso, M. (1999). Functions of the fibrinolytic system in human Ito cells and its control by basic fibroblast and platelet-derived growth factor. Hepatology (Baltimore, Md.), 29(3), 868-78.
Fibbi G, et al. Functions of the Fibrinolytic System in Human Ito Cells and Its Control By Basic Fibroblast and Platelet-derived Growth Factor. Hepatology. 1999;29(3):868-78. PubMed PMID: 10051491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functions of the fibrinolytic system in human Ito cells and its control by basic fibroblast and platelet-derived growth factor. AU - Fibbi,G, AU - Pucci,M, AU - Grappone,C, AU - Pellegrini,G, AU - Salzano,R, AU - Casini,A, AU - Milani,S, AU - Del Rosso,M, PY - 1999/3/3/pubmed PY - 1999/3/3/medline PY - 1999/3/3/entrez SP - 868 EP - 78 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 29 IS - 3 N2 - During liver fibrogenesis, hepatic stellate cells (HSC) proliferate and migrate under the influence of growth factors, including platelet-derived growth factor (PDGF) and basic-fibroblast growth factor (b-FGF). The plasminogen activation system regulates extracellular matrix (ECM) catabolism and cell movement. We evaluated the expression and biological functions of the plasminogen activation system in human HSC and its interaction with PDGF and b-FGF. Urokinase-plasminogen activator receptors (u-PAR) were measured by radioligand binding, cell cross-linking, immunoassay, and RNAse protection assay. u-PA and plasminogen activator inhibitors (PAIs) expression and activities were analyzed by zymography, immunoassay, and RNase protection assay. Cell migration and proliferation, studied in Boyden chambers and by microscopic counting, were evaluated after the addition of PDGF, b-FGF, and blockade with anti-u-PA, anti-u-PAR antibodies, and antisense oligodeoxynucleotides (aODN) against u-PAR mRNA. We have shown that HSC produce u-PAR, u-PA, and PAI-1. PDGF and b-FGF up-regulate u-PA and u-PAR, but not PAI-1, and exogenous addition of u-PA stimulates HSC proliferation, chemotaxis, and chemoinvasion. Inhibition of u-PA/u-PAR with antibodies against u-PA or u-PAR and with u-PAR aODN inhibit the proliferative, chemotactic, and chemoinvasive activity of PDGF and b-FGF. These findings indicate that u-PA and u-PAR are required for the mitogenic and chemoinvasive activity of PDGF and b-FGF on HSC. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/10051491/Functions_of_the_fibrinolytic_system_in_human_Ito_cells_and_its_control_by_basic_fibroblast_and_platelet_derived_growth_factor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270913999001317 DB - PRIME DP - Unbound Medicine ER -