Modulation of Urokinase-Type Plasminogen Activator by Transforming Growth Factor β1 in Acetaldehyde-Activated Hepatic Stellate Cells

Pharmacology ◽  
2004 ◽  
Vol 73 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Georgina Pérez-Liz ◽  
Jorge Flores-Hernández ◽  
José-Antonio Arias-Montaño ◽  
Jorge-Alberto Reyes-Esparza ◽  
Lourdes Rodríguez-Fragoso
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Activated Hepatic Stellate Cells

scholarly journals Smads 2 and 3 Are Differentially Activated by Transforming Growth Factor-β (TGF-β) in Quiescent and Activated Hepatic Stellate Cells

2003 ◽  
Vol 278 (13) ◽  
pp. 11721-11728 ◽  
Author(s):  
Chenghai Liu ◽  
Marianna D. A. Gaça ◽  
E. Scott Swenson ◽  
Vincent F. Vellucci ◽  
Michael Reiss ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Activated Hepatic Stellate Cells

Transforming growth factor-β induces contraction of activated hepatic stellate cells

2004 ◽  
Vol 41 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Kusum K. Kharbanda ◽  
David D. Rogers ◽  
Todd A. Wyatt ◽  
Michael F. Sorrell ◽  
Dean J. Tuma
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Activated Hepatic Stellate Cells

Cellular crosstalk mediated by platelet-derived growth factor BB and transforming growth factor β during hepatic injury activates hepatic stellate cells

2018 ◽  
Vol 96 (8) ◽  
pp. 728-741 ◽  
Author(s):  
Sowmya Mekala ◽  
SubbaRao V. Tulimilli ◽  
Ramasatyaveni Geesala ◽  
Kanakaraju Manupati ◽  
Neha R. Dhoke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Platelet Derived Growth Factor ◽  
Hepatic Tissue

Apoptotic hepatocytes release factors that activate hepatic stellate cells (HSCs), thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride, or thioacetamide. Histology of hepatotoxicant-induced diseased hepatic tissue correlated with differential expression of fibrosis-related genes. A marked increase in co-staining of transforming growth factor β receptor type II (TGFRIIβ) – desmin or α-smooth muscle actin – platelet-derived growth factor receptor β (PDGFRβ), markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V – cytokeratin expressing hepatocytes. To understand the molecular mechanisms of disease pathology, in vitro experiments were designed using the conditioned medium (CM) of hepatotoxicant-treated HepG2 cells supplemented to HSCs. A significant increase in HSC proliferation, migration, and expression of fibrosis-related genes and protein was observed, thereby suggesting the characteristics of an activated phenotype. Treating HepG2 cells with hepatotoxicants resulted in a significant increase in mRNA expression of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ). CM supplemented to HSCs resulted in increased phosphorylation of PDGFRβ and TGFRIIβ along with its downstream effectors, extracellular signal-related kinase 1/2 and focal adhesion kinase. Neutralizing antibodies against PDGF-BB and TGFβ effectively perturbed the hepatotoxicant-treated HepG2 cell CM-induced activation of HSCs. This study suggests PDGF-BB and TGFβ as potential molecular targets for developing anti-fibrotic therapeutics.

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