Exploitation of the hepatic stellate cell Raman signature for their detection in native tissue samples

2014 ◽  
Vol 6 (10) ◽  
pp. 946-956 ◽  
Author(s):  
Kerstin Galler ◽  
Franziska Schleser ◽  
Esther Fröhlich ◽  
Robert Pascal Requardt ◽  
Andreas Kortgen ◽  
...  
Keyword(s):  
Raman Spectra ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Living Tissue ◽  
Tissue Samples ◽  
Native Tissue ◽  
Unique Information

The unique information concentrated in Raman spectra serves to differentiate hepatic stellate cells from hepatocytes, detect them in living tissue and provide insight in their activation state.

scholarly journals Identification of GDF15 as A Pro-Fibrotic Factor in Mouse Liver Fibrosis Progression

2021 ◽  
Author(s):  
Peng Qi ◽  
Ming-Ze Ma ◽  
Jing-Hua Kuai
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Liver Tissue ◽  
Cell Activation ◽  
Stellate Cell ◽  
Neutralizing Antibody ◽  
Stellate Cells ◽  
Fibrosis Progression

Abstract Aim:To elucidate the inhibitory role of growth differentiation factor 15 (GDF15) in liver fibrosis and its possible activation mechanism in hepatic stellate cells of mice.Methods:We generated a GDF15-neutralizing antibody that can inhibit TGF-β1-induced activation of the TGF-β/Smad2/3 pathway in LX-2 cells. All the mice in this study were induced by carbon tetrachloride and thioacetamide. In addition, primary hepatic stellate cells from mice were isolated from fresh livers using Nycodenz density gradient separation. The severity and extent of liver fibrosis in mice were evaluated by Sirius Red and Masson staining. The effect of GDF15 on the activation of the TGF-β pathway was detected using dual-luciferase reporter assays and Western blotting assays.Results:The expression of GDF15 in cirrhotic liver tissue was higher than that in normal liver tissue. Blocking GDF15 with a neutralizing antibody resulted in a delay in primary hepatic stellate cell activation and remission of liver fibrosis induced by carbon tetrachloride or thioacetamide. Meanwhile, TGF-β pathway activation was partly inhibited by a GDF15-neutralizing antibody in primary hepatic stellate cells. These results indicated that GDF15 plays an important role in regulating HSC activation and liver fibrosis progression.Conclusions:The inhibition of GDF15 attenuates chemical-inducible liver fibrosis and delays hepatic stellate cell activation, and this effect is probably mainly attributed to its regulatory role in TGF-β signalling.

Lycopene inhibits hepatic stellate cell activation and modulates cellular lipid storage and signaling

2019 ◽  
Vol 10 (4) ◽  
pp. 1974-1984 ◽  
Author(s):  
Monique de Barros Elias ◽  
Felipe Leite Oliveira ◽  
Fatima Costa Rodrigues Guma ◽  
Renata Brum Martucci ◽  
Radovan Borojevic ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Lipid Storage ◽  
Cellular Lipid ◽  
Perivascular Cells ◽  
Hepatic Stellate Cell Activation

Hepatic stellate cells are liver-specific perivascular cells, identified as the major source of collagen in liver fibrosis, following their activation and conversion to myofibroblast-like cells.

scholarly journals Proliferation of hepatic stellate cells, mediated by YAP and TAZ, contributes to liver repair and regeneration after liver ischemia-reperfusion injury

2018 ◽  
Vol 314 (4) ◽  
pp. G471-G482 ◽  
Author(s):  
Takanori Konishi ◽  
Rebecca M. Schuster ◽  
Alex B. Lentsch
Keyword(s):  
Cell Proliferation ◽  
Liver Injury ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Ischemia Reperfusion ◽  
Stellate Cells ◽  
Hepatocyte Proliferation ◽  
Binding Motif ◽  
Liver Repair

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key regulators of cell proliferation and organ size; however, their physiological contribution after liver injury has not been fully understood. In this study, we sought to determine the role of YAP and TAZ during liver recovery after ischemia-reperfusion (I/R). A murine model of partial (70%) I/R was used to induce liver injury and study the reparative and regenerative response. After liver injury, there was marked activation and proliferation of hepatic stellate cells. The Hippo pathway components, large tumor suppressor 1 (LATS1) and its adapter protein, Mps one binder 1 (MOB1), were inactivated during liver repair, and YAP and TAZ were activated selectively in hepatic stellate cells. Concurrently, the expression of connective tissue growth factor and survivin, both of which are YAP and TAZ target genes, were upregulated. Hepatic stellate cell expansion and concomitant activation of YAP and TAZ occurred only in the injured liver and were not observed in the nonischemic liver. Treatment of mice with verteporfin, an inhibitor of YAP and TAZ, decreased hepatic stellate cell proliferation, survivin, and cardiac ankyrin repeat protein expression. These changes were associated with a significant decrease in hepatocyte proliferation. The data suggest that liver repair and regeneration after I/R injury are dependent on hepatic stellate cell proliferation, which is mediated by YAP and TAZ. NEW & NOTEWORTHY This study is the first to assess the proliferation of hepatic stellate cells (HSCs) after ischemia-reperfusion (I/R) injury and their role in the reparative and regenerative process. Here we show that the Hippo pathway is inactivated after I/R and that Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) activation is detected in HSC. HSC proliferation and expansion are prominent during liver recovery after I/R injury. Inhibition of YAP/TAZ activation with verteporfin reduces HSC proliferation and target gene expression and attenuates hepatocyte proliferation.

scholarly journals Dysregulation of miR-21-associated miRNA regulatory networks by chronic ethanol consumption impairs liver regeneration

2021 ◽  
Author(s):  
Austin Parrish ◽  
Ankita Srivastava ◽  
Egle Juskeviciute ◽  
Jan B. Hoek ◽  
Rajanikanth Vadigepalli
Keyword(s):  
Liver Regeneration ◽  
Hepatic Stellate Cell ◽  
Mirna Expression ◽  
Hepatic Stellate Cells ◽  
Regulatory Networks ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Chronic Ethanol ◽  
Regenerative Capacity

Impaired liver regeneration has been considered as a hallmark of progression of alcohol-associated liver disease. Our previous studies demonstrated that in vivo inhibition of the microRNA (miRNA) miR21 can restore regenerative capacity of the liver in chronic ethanol-fed animals. The present study focuses on the role of microRNA regulatory networks that are likely to mediate the miR-21 action. Rats were chronically fed an ethanol-enriched diet along with pair-fed control animals and treated with AM21 (anti-miR-21), a locked nucleic acid antisense to miR-21. Partial hepatectomy (PHx) was performed and miRNA expression profiling over the course of liver regeneration was assessed. Our results showed dynamic expression changes in several miRNAs post PHx, notably with altered miRNA expression profiles between ethanol versus control groups. We found that in vivo inhibition of miR-21 led to correlated differential expression of miR-340-5p, and anti-correlated expression of miR-365, let-7a, miR-1224 and miR-146a across all sample groups post PHx. Gene set enrichment analysis identified a miRNA signature significantly associated with hepatic stellate cell activation within whole-liver tissue data. We hypothesized that at least part of the PHx-induced miRNA network changes responsive to miR-21 inhibition is localized to hepatic stellate cells. We validated this hypothesis using AM21 and TGF-β treatments in LX-2 human hepatic stellate cells in culture, and measured expression levels of select miRNAs by quantitative RT-PCR. Based on the in vivo and in vitro results, we propose a hepatic stellate cell miRNA regulatory network as contributing to the restoration of liver regenerative capacity by miR-21 inhibition.

Rat hepatic stellate cell expression of α2-macroglobulin is a feature of cellular activation: implications for matrix remodelling in hepatic fibrosis

1998 ◽  
Vol 95 (2) ◽  
pp. 179-186 ◽  
Author(s):  
C. A. KAWSER ◽  
J. P. IREDALE ◽  
P. J. WINWOOD ◽  
M. J. P. ARTHUR
Keyword(s):  
Protease Inhibitor ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Northern Analysis ◽  
Control Value ◽  
Α2 Macroglobulin ◽  
Cell Expression

1.Hepatic stellate cells are key mediators of hepatic fibrosis. We have studied hepatic stellate cell expression of the collagenase and general protease inhibitor α2-macroglobulin after activation in tissue culture and in response to certain cytokines. 2.Hepatic stellate cells isolated by Pronase–collagenase digestion were activated by culture on uncoated plastic. By Northern analysis hepatic stellate cells undergoing activation (5 days) expressed α2-macroglobulin mRNA and α2-macroglobulin could be immunolocalized to hepatic stellate cells from 5 to 15 days of culture. 3.By ELISA of cell culture supernatants hepatic stellate cell secretion of α2-macroglobulin was found to increase from 2.78±1.13 ;ng·ml-1·μg-1 DNA per 24 ;h at 5 days of culture (n = 8) to 13.55±4.64 ;ng·ml-1·μg-1 DNA per 24 ;h at 15 days of culture (n = 7). Stimulation of hepatic stellate cells with interleukin-6 at 5 days caused a significant increase in α2-macroglobulin expression as did exposure to Kupffer-cell conditioned medium. However, exposure of hepatic stellate cells to interleukin-1, transforming growth factor-β1 and tumour necrosis factor-α had no significant effect. 4.During profibrotic liver injury plasma α2-macroglobulin levels were found to increase to between 850% and 250% of the control value (100%) after bile duct ligation (72 ;h to 13 days respectively), and to 1166% and 1106% of the control value during progressive CCl4-induced fibrosis (24 ;h to 4 weeks respectively). 5.These data suggest that hepatic stellate cells are a potential source of the potent protease inhibitor α2-macroglobulin, expression of which may inhibit matrix remodelling during progressive fibrosis.

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