scholarly journals Transcriptional Dynamics of Hepatic Sinusoid‐Associated Cells After Liver Injury

Hepatology ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 2119-2133 ◽  
Author(s):  
Mike K. Terkelsen ◽  
Sofie M. Bendixen ◽  
Daniel Hansen ◽  
Emma A.H. Scott ◽  
Andreas F. Moeller ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Sinusoid ◽  
Transcriptional Dynamics

scholarly journals Hepatic sinusoidal endothelium avidly binds platelets in an integrin-dependent manner, leading to platelet and endothelial activation and leukocyte recruitment

2013 ◽  
Vol 304 (5) ◽  
pp. G469-G478 ◽  
Author(s):  
Patricia F. Lalor ◽  
John Herbert ◽  
Roy Bicknell ◽  
David H. Adams
Keyword(s):  
Endothelial Cells ◽  
Liver Injury ◽  
Leukocyte Adhesion ◽  
Endothelial Activation ◽  
Dependent Manner ◽  
Hepatic Sinusoid ◽  
Public Expression ◽  
Platelet Binding ◽  
Sinusoidal Endothelium ◽  
Functional Relevance

Platelets have recently been shown to drive liver injury in murine models of viral hepatitis and promote liver regeneration through the release of serotonin. Despite their emerging role in inflammatory liver disease, little is known about the mechanisms by which platelets bind to the hepatic vasculature. Therefore, we referenced public expression data to determine the profile of potential adhesive receptors expressed by hepatic endothelium. We then used a combination of tissue-binding and flow-based endothelial-binding adhesion assays to show that resting platelets bind to human hepatic sinusoidal endothelial cells and that the magnitude of adhesion is greatly enhanced by thrombin-induced platelet activation. Adhesion was mediated by the integrins Gp1b, αIIbβIII, and αvβ3, as well as immobilized fibrinogen. Platelet binding to hepatic endothelial cells resulted in NF-κB activation and increased chemokine secretion. The functional relevance of platelet binding was confirmed by experiments that showed markedly increased binding of neutrophils and lymphocytes to hepatic endothelial cells under shear conditions replicating those found in the hepatic sinusoid, which was in part dependent on P-selectin expression. Thus the ability of platelets to activate endothelium and promote leukocyte adhesion may reflect an additional mechanism through which they promote liver injury.

Hydrogen sulfide modulates sinusoidal constriction and contributes to hepatic micorcirculatory dysfunction during endotoxemia

2013 ◽  
Vol 304 (12) ◽  
pp. G1070-G1078 ◽  
Author(s):  
Eric J. Norris ◽  
Nicole Feilen ◽  
Nhat H. Nguyen ◽  
Cathy R. Culberson ◽  
Min C. Shin ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Liver Injury ◽  
Portal Pressure ◽  
Hepatic Microcirculation ◽  
Hepatic Sinusoid ◽  
Microcirculatory Dysfunction ◽  
Nadh Fluorescence ◽  
Vasoconstrictor Effect ◽  
Portal Infusion

Hydrogen sulfide (H2S) affects vascular resistance; however, its effect on the hepatic microcirculation has not been investigated. Hepatic sinusoidal perfusion is dysregulated during sepsis, contributing to liver injury. Therefore, the present study determined the effect of H2S on the hepatic microcirculation and the contribution of endogenous H2S to hepatic microcirculatory dysfunction in an endotoxin model of sepsis. Portal infusion of H2S increased portal pressure in vivo (6.8 ± 0.2 mmHg before H2S vs. 8.6 ± 0.8 mmHg peak during H2S infusion, P < 0.05). Using intravital microscopy, we observed decreased sinusoidal diameter (6.2 ± 0.27 μm before H2S vs. 5.7 ± 0.3 μm after H2S, P < 0.05) and increased sinusoidal heterogeneity during H2S infusion ( P < 0.05) and net constriction. Since hepatic H2S levels are elevated during sepsis, we used the cystathionine γ lyase inhibitor dl-propargylglycine (PAG) to determine the contribution of H2S to the hypersensitization of the sinusoid to the vasoconstrictor effect of endothelin-1 (ET-1). PAG treatment significantly attenuated the sinusoidal sensitization to ET-1 in endotoxin-treated animals. ET-1 infusion increased portal pressure to 175% of baseline in endotoxemic animals, which was reduced to 143% following PAG treatment ( P < 0.05). PAG abrogated the increase in sinusoidal constriction after ET-1 infusion in LPS-treated rats (30.9% reduction in LPS rats vs. 11.6% in PAG/LPS rats, P < 0.05). Moreover, PAG treatment significantly attenuated the increase in NADH fluorescence following ET-1 exposure during endotoxemia (61 grayscale units LPS vs. 21 units in PAG/LPS, P < 0.05), suggesting an improvement in hepatic oxygen availability. This study is the first to demonstrate a vasoconstrictor action of H2S on the hepatic sinusoid and provides a possible mechanism for the protective effect of PAG treatment during sepsis.

Effects of Steroids on Fetal Rat Liver

1969 ◽  
Vol 27 ◽  
pp. 350-351
Author(s):  
F. G. Zaki
Keyword(s):  
Liver Injury ◽  
Rat Liver ◽  
Fetal Liver ◽  
Dosage Level ◽  
Maternal Plasma ◽  
Methyl Prednisolone ◽  
Fetal Rat ◽  
Toxic Agents ◽  
Fetal Rat Liver ◽  
Neonatal Liver

Fetal and neonatal liver injury induced by agents circulating in maternal plasma, even though well recognized, its morphological manifestations are not yet established. As part of our studies of fetal and neonatal liver injury induced by maternal nutritional disorders, metabolic impairment and toxic agents, the effects of two anti-inflammatory steroids have been recently inves tigated.Triamcinolone and methyl prednisolone were injected each in a group of rats during pregnancy at a-dosage level of 2 mgm three times a week. Fetal liver was studied at 18 days of gestation. Litter size and weight markedly decreased than those of control rats. Stillbirths and resorption were of higher incidence in the triamcinolone group than in those given the prednisolone.

Proteinase activated receptor (PAR)-2 agonistic peptide protects from Th-1 mediated liver injury in mice

2001 ◽  
Vol 120 (5) ◽  
pp. A27-A27
Author(s):  
S FLORUCCI ◽  
A MENCARELLI ◽  
B PALAZZETTI ◽  
E DISTRUTTI ◽  
G CIRINO ◽  
...  
Keyword(s):  
Liver Injury ◽  
Th 1

Toll-like receptor 2 signaling is important for fas ligand on NKT cells, may contribute to liver injury induced by Salmonella infection

2001 ◽  
Vol 120 (5) ◽  
pp. A357-A357
Author(s):  
H SHIMIZU ◽  
Y FUKUDA ◽  
I NAKANO ◽  
Y KATANO ◽  
K NAGANO ◽  
...  
Keyword(s):  
Liver Injury ◽  
Fas Ligand ◽  
Nkt Cells ◽  
Toll Like Receptor ◽  
Salmonella Infection ◽  
Toll Like Receptor 2

Oral contraceptives worsen endotoxin induced liver injury in rats

2001 ◽  
Vol 120 (5) ◽  
pp. A116-A116
Author(s):  
A KONNO ◽  
N ENOMOTO ◽  
M HIROSE ◽  
K IKEJIMA ◽  
S MATSUYAMA ◽  
...  
Keyword(s):  
Liver Injury ◽  
Oral Contraceptives

Alterations of Glucose Metabolism in Viral and Toxic Liver Injury

1964 ◽  
Vol 46 (4) ◽  
pp. 424-433 ◽  
Author(s):  
Kurt J. Isselbacher ◽  
Wallace A. Jones
Keyword(s):  
Glucose Metabolism ◽  
Liver Injury ◽  
Toxic Liver Injury
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