Inhibition of PDGF signaling promotes hepatic differentiation of stellate cells from rat liver

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
D Reichert ◽  
L Adolph ◽  
J Köhler ◽  
C Kordes ◽  
D Häussinger
Keyword(s):  
Rat Liver ◽  
Stellate Cells ◽  
Hepatic Differentiation ◽  
Pdgf Signaling

scholarly journals Portal hypertensive response to kinin

2009 ◽  
Vol 81 (3) ◽  
pp. 431-442 ◽  
Author(s):  
Maria Kouyoumdjian ◽  
Marcia R. Nagaoka ◽  
Mauricio R. Loureiro-Silva ◽  
Durval R. Borges
Keyword(s):  
Vascular Resistance ◽  
Rat Liver ◽  
Liver Perfusion ◽  
Stellate Cells ◽  
Kinin System ◽  
Rat Liver Perfusion ◽  
Isolated Liver Cells ◽  
B2 Receptors ◽  
Intrahepatic Vascular Resistance

Portal hypertension is the most common complication of chronic liver diseases, such as cirrhosis. The increased intrahepatic vascular resistance seen in hepatic disease is due to changes in cellular architecture and active contraction of stellate cells. In this article, we review the historical aspects of the kallikrein-kinin system, the role of bradykinin in the development of disease, and our main findings regarding the role of this nonapeptide in normal and experimentalmodels of hepatic injury using the isolated rat liver perfusion model (mono and bivascular) and isolated liver cells. We demonstrated that: 1) the increase in intrahepatic vascular resistance induced by bradykinin is mediated by B2 receptors, involving sinusoidal endothelial and stellate cells, and is preserved in the presence of inflammation, fibrosis, and cirrhosis; 2) the hepatic arterial hypertensive response to bradykinin is calcium-independent and mediated by eicosanoids; 3) bradykinin does not have vasodilating effect on the pre-constricted perfused rat liver; and, 4) after exertion of its hypertensive effect, bradykinin is degraded by angiotensin converting enzyme. In conclusion, the hypertensive response to BK is mediated by the B2 receptor in normal and pathological situations. The B1 receptor is expressed more strongly in regenerating and cirrhotic livers, and its role is currently under investigation.

Hepatic Stellate Cells Play a Functional Role in Exacerbating Ischemia-Reperfusion Injury in Rat Liver

2019 ◽  
Vol 60 (1-2) ◽  
pp. 74-85 ◽  
Author(s):  
Tomokazu Takahashi ◽  
Masato Yoshioka ◽  
Hiroshi Uchinami ◽  
Yasuhiko Nakagawa ◽  
Naohiko Otsuka ◽  
...  
Keyword(s):  
Rat Liver ◽  
Hepatic Stellate Cells ◽  
Functional Role ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Stellate Cells ◽  
Treated Group ◽  
Sprague Dawley ◽  
Perfusion Rate ◽  
Sprague Dawley Rats

Purpose: The involvement of hepatic stellate cells (HSCs) with ischemia-reperfusion (I/R) injury in rat liver was examined using gliotoxin, which is known to induce HSC apoptosis. Methods: Male Sprague-Dawley rats were used. HSC was represented by a glial fibrillary acidic protein (GFAP)-positive cell. Liver ischemia was produced by cross-clamping the hepatoduodenal ligament. The degree of I/R injury was evaluated by a release of aminotransferases. Sinusoidal diameter and sinusoidal perfusion rates were examined using intravital fluorescence microscopy. Results: Gliotoxin significantly decreased the number of GFAP-positive cells 48 h after dosing (2.50 ± 0.19% [mean ± SD] in the nontreated group vs. 1.91 ± 0.46% in the gliotoxin-treated group). Liver damage was significantly suppressed by the pretreatment with gliotoxin. Sinusoidal diameters in zone 3 were wider in the gliotoxin group (10.25 ± 0.35 µm) than in the nontreated group (8.21 ± 0.50 µm). The sinusoidal perfusion rate was maintained as well in the gliotoxin group as in normal livers, even after I/R. Conclusions: Pretreatment with gliotoxin significantly reduced the number of HSCs in the liver and further suppressed liver injury following I/R. It is strongly suggested that HSCs play a functional role in exacerbating the degree of I/R injury of the liver.

scholarly journals Apoprotein-independent binding of chylomicron remnants to rat liver membranes

1991 ◽  
Vol 279 (3) ◽  
pp. 769-773 ◽  
Author(s):  
J Borensztajn ◽  
T J Kotlar ◽  
S Y Chang
Keyword(s):  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Hepatic Differentiation ◽  
Direct Role ◽  
Isolated Rat Liver ◽  
Liver Membranes ◽  
Chylomicron Remnants ◽  
Isolated Rat

Rat lymph chylomicrons and chylomicron remnants were treated with trypsin or Pronase. The ability of the resulting apoprotein-free lipoproteins to be taken up by the isolated perfused rat liver, and to bind to isolated rat liver membranes, was examined. Compared with control lipoproteins, the apoprotein-free chylomicrons and remnants retained unaltered their capacity to be differentiated by the intact liver and by the isolated membranes. Further, control remnants and apoprotein-free remnants competed for binding to the isolated membranes. We conclude that apoproteins are not required for the hepatic differentiation between chylomicrons and remnants, and suggest that the lipoprotein phospholipids may play a direct role in this process.

scholarly journals Differential regulation of TGF-β signal in hepatic stellate cells between acute and chronic rat liver injury

Hepatology ◽  
2002 ◽  
Vol 35 (1) ◽  
pp. 49-61 ◽  
Author(s):  
Yoshiya Tahashi ◽  
Koichi Matsuzaki ◽  
Masataka Date ◽  
Katsunori Yoshida ◽  
Fukiko Furukawa ◽  
...  
Keyword(s):  
Liver Injury ◽  
Rat Liver ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Differential Regulation

Rat liver myofibroblasts and hepatic stellate cells: Different cell populations of the fibroblast lineage with fibrogenic potential

1999 ◽  
Vol 117 (5) ◽  
pp. 1205-1221 ◽  
Author(s):  
Thomas Knittel ◽  
Dominik Kobold ◽  
Bernhard Saile ◽  
Anka Grundmann ◽  
Katrin Neubauer ◽  
...  
Keyword(s):  
Rat Liver ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Cell Populations ◽  
Liver Myofibroblasts

scholarly journals A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yang Xu ◽  
Zhangxiao Peng ◽  
Weidan Ji ◽  
Xiang Li ◽  
Xuejing Lin ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Rat Liver ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Critical Event ◽  
Pharmacological Activities ◽  
Fibrosis Progression ◽  
Collagen Iii ◽  
Rat Liver Fibrosis ◽  
Low Toxicity

Activation of hepatic stellate cells (HSCs) is a critical event in process of hepatic fibrogenesis and cirrhosis. Matrine, the active ingredient ofSophora, had been used for clinical treatment of acute/chronic liver disease. However, its potency was low. We prepared a high potency and low toxicity matrine derivate, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities on antihepatic fibrosis. This study demonstrated that WM130 results in a decreased proliferative activity of HSC-T6 cells, with the half inhibitory concentration (IC50) of 68 μM. WM130 can inhibit the migration and induce apoptosis in HSC-T6 cells at both concentrations of 68 μM (IC50) and 34 μM (half IC50). The expression ofα-SMA, Collagen I, Collagen III, and TGF-β1 could be downregulated, and the protein phosphorylation levels of EGFR, AKT, ERK, Smad, and Raf (p-EGFR, p-AKT, p-ERK, p-Smad, and p-Raf) were also decreased by WM130. On the DMN-induced rat liver fibrosis model, WM130 can effectively reduce the TGF-β1, AKT,α-SMA, and p-ERK levels, decrease the extracellular matrix (ECM) formation, and inhibit rat liver fibrosis progression. In conclusion, this study demonstrated that WM130 can significantly inhibit the activation of HSC-T6 cells and block the rat liver fibrosis progression by inducing apoptosis, suppressing the deposition of ECM, and inhibiting TGF-β/Smad and Ras/ERK pathways.

Influence of caveolin on constitutively activated recombinant eNOS: insights into eNOS dysfunction in BDL rat liver

2003 ◽  
Vol 285 (3) ◽  
pp. G652-G660 ◽  
Author(s):  
H. Hendrickson ◽  
S. Chatterjee ◽  
S. Cao ◽  
M. Morales Ruiz ◽  
W. C. Sessa ◽  
...  
Keyword(s):  
Rat Liver ◽  
Hepatic Stellate Cells ◽  
Fluorescent Protein ◽  
Stellate Cell ◽  
Active Form ◽  
Stellate Cells ◽  
Liver Cells ◽  
No Production

Diminished endothelial nitric oxide (NO) synthase (eNOS)-derived NO production from the hepatic vascular endothelium contributes to hepatic vasoconstriction in portal hypertension. The aim of this study was to examine the mechanism of this process by testing the influence of a constitutively active form of eNOS (S1179DeNOS) in both primary and propagated liver cells in vitro and in the sham and bile duct ligated (BDL) rat liver in vivo, using an adenoviral vector encoding green fluorescent protein (AdGFP) and S1179DeNOS (AdS1179DeNOS). AdS1179DeNOS transduction augmented basal and agonist-stimulated NO generation in nonparenchymal liver cells. Sham rats transduced in vivo with AdS1179DeNOS evidenced a decreased pressor response to incremental doses of the vasoconstrictor methoxamine compared with sham rats transduced with AdGFP. However, BDL rats transduced with AdS1179DeNOS did not display improved vasodilatory responses as evidenced by similar flow-dependent pressure increases to that observed in BDL rats transduced with AdGFP, despite similar levels of viral transgene expression. We next examined the influence of the eNOS inhibitory protein caveolin on S1179DeNOS dysfunction in cirrhotic liver. Immunogold electron microscopic analysis of caveolin in BDL liver demonstrated prominent expression not only in liver endothelial cells, but also in hepatic stellate cells. In vitro studies in the LX2 hepatic stellate cell line demonstrate that caveolin precipitates recombinant S1179DeNOS in LX2 cells, that recombinant S1179DeNOS coprecipitates caveolin, and that binding is enhanced in the presence of overexpression of caveolin. Furthermore, caveolin overexpression inhibits recombinant S1179DeNOS activity. These studies indicate that recombinant S1179DeNOS protein functions appropriately in normal liver cells and tissue but evidences dysfunction in the cirrhotic rat liver and that caveolin expression and inhibition in BDL nonparenchymal cells, including hepatic stellate cells, may account for this dysfunction.

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