scholarly journals Targeted inhibition of platelet-derived growth factor receptor-β subunit in hepatic stellate cells ameliorates hepatic fibrosis in rats

Gene Therapy ◽  
2008 ◽  
Vol 15 (21) ◽  
pp. 1424-1435 ◽  
Author(s):  
S-W Chen ◽  
Y-X Chen ◽  
X-R Zhang ◽  
H Qian ◽  
W-Z Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Growth Factor Receptor ◽  
Stellate Cells ◽  
Platelet Derived Growth Factor ◽  
Β Subunit ◽  
Targeted Inhibition

scholarly journals Non-Invasively Distinguishing Progress of Liver Fibrosis by Visualizing Hepatic Platelet Derived Growth Factor Receptor-Beta Expression with an MRI Modality in Mice

2020 ◽  
Author(s):  
Ling Wu ◽  
Xiao-quan Huang ◽  
Na Li ◽  
Cao Xie ◽  
Sheng-xiang Rao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Cyclic Peptides ◽  
Growth Factor Receptor ◽  
Stellate Cells ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner ◽  
Activated Hepatic Stellate Cells

Abstract Background: Activated hepatic stellate cells are the most critical cell responsible for liver fibrosis. In liver fibrogenesis, platelet-derived growth factor is the most prominent mitogen for hepatic stellate cells. This study aims to explore the potential of gadolinium (Gd)-labeled cyclic peptides (pPB) targeted to platelet-derived growth factor receptor-β (PDGFR-β) as a magnetic resonance imaging (MRI) radiotracer to identify the progress of liver fibrosis by imaging hepatic PDGFR-β expression. Results: Hepatic PDGFR-β expression level was found to be paralleled with the severity of liver fibrosis, which was increased with the progression of fibrosis and reduced with the regression. Majority of cells expressing PDGFR-β was determined to be activated hepatic stellate cells in fibrotic livers. Culture-activated human hepatic stellate cells expressed abundant PDGFR-β, and FITC-labeled pPB could bind to human hepatic stellate cells in a concentration and time dependent manner. With Gd-labeled pPB as a tracer, an MRI modality demonstrated that the relative hepatic T1-weighed MR signal value was increased progressively along with severity of hepatic fibrosis and reduced with the remission. Conclusion: Hepatic PDGFR-β expression reflects the progress of hepatic fibrosis, and MR imaging using Gd-labeled pPB as a tracer may distinguish different stages of liver fibrosis in mice.

scholarly journals RNA interference targeting the platelet-derived growth factor receptor β subunit ameliorates experimental hepatic fibrosis in rats

2008 ◽  
Vol 28 (10) ◽  
pp. 1446-1457 ◽  
Author(s):  
Si-Wen Chen ◽  
Xing-Rong Zhang ◽  
Chong-Ze Wang ◽  
Wei-Zhong Chen ◽  
Wei-Fen Xie ◽  
...  
Keyword(s):  
Rna Interference ◽  
Growth Factor ◽  
Hepatic Fibrosis ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Β Subunit

scholarly journals Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Si Chen ◽  
Yi Chen ◽  
Bi Chen ◽  
Yi-jing Cai ◽  
Zhuo-lin Zou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Epidermal Growth Factor ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Growth Factor Receptor ◽  
Stellate Cells ◽  
Heparin Binding ◽  
Fibrotic Liver ◽  
Epidermal Growth

Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4treated rats. At concentrations of 2 to 6 μM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF-like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression ofα-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells.

Leptin facilitates proliferation of hepatic stellate cells through up-regulation of platelet-derived growth factor receptor

2004 ◽  
Vol 323 (3) ◽  
pp. 1091-1095 ◽  
Author(s):  
Tie Lang ◽  
Kenichi Ikejima ◽  
Mutsuko Yoshikawa ◽  
Nobuyuki Enomoto ◽  
Katsuyori Iijima ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Growth Factor Receptor ◽  
Stellate Cells ◽  
Platelet Derived Growth Factor

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.

scholarly journals The mitogenic effect of platelet-derived growth factor in human hepatic stellate cells requires calcium influx

1995 ◽  
Vol 269 (5) ◽  
pp. C1133-C1139 ◽  
Author(s):  
P. Failli ◽  
C. Ruocco ◽  
R. De Franco ◽  
A. Caligiuri ◽  
A. Gentilini ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
High Density ◽  
Platelet Derived Growth Factor ◽  
Low Density ◽  
Plateau Phase ◽  
Time Dynamics ◽  
High Density Cell

Platelet-derived growth factor (PDGF) is a key mitogen for hepatic stellate cells (HSC) and has been shown to be implicated in liver tissue repair and fibrogenesis. In this study the relationship between PDGF-induced intracellular Ca2+ concentration ([Ca2+]i) increase and mitogenesis in cultured human HSC was evaluated. In high-density cell cultures (80-90% subconfluence), PDGF induced a significant increase in [Ca2+]i, characterized by a short-lasting peak phase, which was followed by a long-lasting plateau phase. The plateau phase was abolished in the absence of extracellular Ca2+. However, in low-density cell cultures (30-40% subconfluence), the plateau phase was absent or markedly less pronounced. In parallel sets of experiments, PDGF was significantly less effective in inducing mitogenesis in low-density cell cultures than in high-density cell cultures and was totally ineffective in the absence of extracellular Ca2+. These results suggest that 1) spatial and time dynamics of PDGF-induced [Ca2+]i increase are dependent on cell density and 2) PDGF-induced mitogenesis requires extracellular Ca2+ influx.

scholarly journals Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells

2000 ◽  
Vol 119 (2) ◽  
pp. 479-492 ◽  
Author(s):  
Paola Failli ◽  
Raffaella M.S. DeFranco ◽  
Alessandra Caligiuri ◽  
Alessandra Gentilini ◽  
Roberto Giulio Romanelli ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Platelet Derived Growth Factor ◽  
And Migration ◽  
Proliferation And Migration
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