Alteration of pancreatic carcinoma and promyeloblastic cell adhesion in liver microvasculature by co-culture of hepatocytes, hepatic stellate cells and endothelial cells in a physiologically-relevant model

2017 ◽  
Vol 9 (4) ◽  
pp. 350-361 ◽  
Author(s):  
Mathieu Danoy ◽  
Marie Shinohara ◽  
Astia Rizki-Safitri ◽  
Dominique Collard ◽  
Vincent Senez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Pancreatic Carcinoma ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Relevant Model ◽  
Culture Of Hepatocytes

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.

scholarly journals Endothelin-1 in portal hypertension: The intricate role of hepatic stellate cells

2020 ◽  
Vol 245 (16) ◽  
pp. 1504-1512 ◽  
Author(s):  
Devaraj Ezhilarasan
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Portal Hypertension ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chronic Liver ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Endothelin 1 ◽  
Activated Hepatic Stellate Cells

Portal hypertension is one of the most important cirrhosis-associated complications of chronic liver disease, leading to significant morbidity and mortality. After chronic liver injury, hepatic stellate cells reside in the perisinusoidal space activted and acquire a myofibroblast-like phenotype. The activated hepatic stellate cells act as both sources as well as the target for a potent vasoconstrictor endothelin-1. Activation of hepatic stellate cells plays a vital role in the onset of cirrhosis by way of increased extracellular matrix production and the enhanced contractile response to vasoactive mediators such as endothelin-1. In fibrotic/cirrhotic liver, activated hepatic stellate cells produce endothelin-1 leading to an imbalance between pro and antifibrotic factors responsible for enormous extracellular matrix synthesis. Thus, extracellular matrix deposition in the perisinusoidal space further augments liver stiffness and elevates the vascular tone and portal hypertension. Portal hypertension is a complex process modulated by several cell types like hepatic stellate cells, liver sinusoidal endothelial cells, Kupffer cells, injured hepatocytes, immune cells, and biliary epithelial cells. Therefore, targeting a single cell type may not be useful for regression of cirrhosis and portal hypertension. Nevertheless, numerous findings indicate that functionally liver sinusoidal endothelial cells and hepatic stellate cells closely regulate the sinusoidal blood flow via synthesis of several vasoactive molecules including endothelin-1, and hence targeting these cells with novel pharmacological agents may offer promising results. Impact statement Portal hypertension is pathologically defined as increase of portal venous pressure, mainly due to chronic liver diseases such as fibrosis and cirrhosis. In fibrotic liver, activated hepatic stellate cells increase their contraction in response to endothelin-1 (ET-1) via autocrine and paracrine stimulation from liver sinusoidal endothelial cells and injured hepatocytes. Clinical studies are limited with ET receptor antagonists in cirrhotic patients with portal hypertension. Hence, studies are needed to find molecules that block ET-1 synthesis. Accumulation of extracellular matrix proteins in the perisinusoidal space, tissue contraction, and alteration in blood flow are prominent during portal hypertension. Therefore, novel matrix modulators should be tested experimentally as well as in clinical studies. Specifically, tumor necrosis factor-α, transforming growth factor-β1, Wnt, Notch, rho-associated protein kinase 1 signaling antagonists, and peroxisome proliferator-activated receptor α and γ, interferon-γ and sirtuin 1 agonists should be tested elaborately against cirrhosis patients with portal hypertension.

scholarly journals Expression and Regulation of Cell Adhesion Molecules by Hepatic Stellate Cells (HSC) of Rat Liver

1999 ◽  
Vol 154 (1) ◽  
pp. 153-167 ◽  
Author(s):  
Thomas Knittel ◽  
Christina Dinter ◽  
Dominik Kobold ◽  
Katrin Neubauer ◽  
Mirko Mehde ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Rat Liver ◽  
Hepatic Stellate Cells ◽  
Cell Adhesion Molecules ◽  
Stellate Cells

Induction of apoptosis in rat hepatic stellate cells by disruption of integrin-mediated cell adhesion

1999 ◽  
Vol 134 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Hiroaki Iwamoto ◽  
Hironori Sakai ◽  
Seiya Tada ◽  
Makoto Nakamuta ◽  
Hajime Nawata
Keyword(s):  
Cell Adhesion ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Induction Of Apoptosis
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