scholarly journals Induction and contribution of beta platelet-derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice

2015 ◽  
Vol 36 (6) ◽  
pp. 874-882 ◽  
Author(s):  
Peri Kocabayoglu ◽  
David Y. Zhang ◽  
Kensuke Kojima ◽  
Yujin Hoshida ◽  
Scott L. Friedman
Keyword(s):  
Growth Factor ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Platelet Derived Growth Factor ◽  
Growth Factor Signalling

scholarly journals Platelet Interactions with Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells Lead to Hepatocyte Proliferation

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1243 ◽  
Author(s):  
Jeremy Meyer ◽  
Alexandre Balaphas ◽  
Pierre Fontana ◽  
Philippe Morel ◽  
Simon C. Robson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Hepatocyte Proliferation ◽  
Liver Sinusoidal Endothelial Cells ◽  
Hepatocyte Growth

(1) Background: Platelets were postulated to constitute the trigger of liver regeneration. The aim of this study was to dissect the cellular interactions between the various liver cells involved in liver regeneration and to clarify the role of platelets. (2) Methods: Primary mouse liver sinusoidal endothelial cells (LSECs) were co-incubated with increasing numbers of resting platelets, activated platelets, or platelet releasates. Alterations in the secretion of growth factors were measured. The active fractions of platelet releasates were characterized and their effects on hepatocyte proliferation assessed. Finally, conditioned media of LSECs exposed to platelets were added to primary hepatic stellate cells (HSCs). Secretion of hepatocyte growth factor (HGF) and hepatocyte proliferation were measured. After partial hepatectomy in mice, platelet and liver sinusoidal endothelial cell (LSEC) interactions were analyzed in vivo by confocal microscopy, and interleukin-6 (IL-6) and HGF levels were determined. (3) Results: Co-incubation of increasing numbers of platelets with LSECs resulted in enhanced IL-6 secretion by LSECs. The effect was mediated by the platelet releasate, notably a thermolabile soluble factor with a molecular weight over 100 kDa. The conditioned medium of LSECs exposed to platelets did not increase proliferation of primary hepatocytes when compared to LSECs alone but stimulated hepatocyte growth factor (HGF) secretion by HSCs, which led to hepatocyte proliferation. Following partial hepatectomy, in vivo adhesion of platelets to LSECs was significantly increased when compared to sham-operated mice. Clopidogrel inhibited HGF secretion after partial hepatectomy. (4) Conclusion: Our findings indicate that platelets interact with LSECs after partial hepatectomy and activate them to release a large molecule of protein nature, which constitutes the initial trigger for liver regeneration.

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

Effect of phorbol ester and platelet-derived growth factor on protein kinase C in rat hepatic stellate cells

2007 ◽  
Vol 27 (8) ◽  
pp. 1066-1075 ◽  
Author(s):  
Yoshimasa Kobayashi ◽  
Kim R. Bridle ◽  
Grant A. Ramm ◽  
Rosemary O'Neill ◽  
Robert S. Britton ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Platelet Derived Growth Factor ◽  
Kinase C
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