Signal transduction in hepatic stellate cells

Pinzani, Massimo; Marra, Fabio; Carloni, Vinicio

doi:10.1111/j.1600-0676.1998.tb00120.x

Cited by 218 publications

(80 citation statements)

References 69 publications

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“…It has been shown that inflammatory molecular events are regulated following activation of NF-κB by CCl 4 release of these cytokines (Weber et al, 2003). Because NF-κB is a cardinal regulator of inflammatory response, controlling the expression of genes encoding cytokines (Pinzani et al, 1998;Muriel, 2007b), inhibition of this factor by curcumin has been performed to prevent acute (Reyes-Gordillo et al, 2007) and chronic liver injury (Bruck et al, 2007). In the case of acute CCl 4 -induced hepatic damage, Reyes-Gordillo et al (2007) observed that intoxication with this agent increased serum markers of damage and distorted the tissue parenchyma.…”

Section: Curcumin and Liver Damagementioning

confidence: 99%

NF‐κB in liver diseases: a target for drug therapy

Muriel

2008

J of Applied Toxicology

148

106

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There are five nuclear factor-kB (NF-kB) transcription factors with important roles in innate immunity, liver inflammation, fibrosis and apoptosis prevention. Several inhibitors of NF-kB, like caffeic acid, captopril, curcumin, pyrrolidine dithiocarbamate, resveratrol, silymarin and thalidomide, have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the liver. A link between inflammation and hepatocellular carcinoma through the NF-kB pathway has been observed, providing ample experimental support for the tumor-promoting function of NF-kB in various models of cancer. NF-kB has been associated with the induction of proinflammatory gene expression and has attracted interest as a target for the treatment of inflammatory disease. However, despite much attention being focused on the deleterious effects of NF-kB, activation of this factor during the resolution of inflammation is associated with the production of antiinflammatory molecules like interleukin (IL)-10 and the onset of apoptosis. This suggests that NF-kB has an antiinflammatory role in vivo involving the regulation of the resolution of inflammation. Also, NF-kB promotes liver regeneration by upregulating IL-6 and other molecules like hepatocyte growth factor. It has been postulated that the beneficial properties of NF-kB are due to p50 homodimers, whose activation prevents cholestatic and chronic liver injury. More basic understanding on the function of the diverse NF-kB factors is urgently needed in different physiological and pathological conditions, because depending on the subunit composition of the dimmer, the disease and the stage of the illness, inhibition of the factor may result in a beneficial or in a deleterious response. Copyright © 2008 John Wiley & Sons, Ltd.There are five nuclear factor-kB (NF-kB) transcription factors with important roles in innate immunity, liver inflammation, fibrosis, and apoptosis prevention. Several inhibitors of NF-kB have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the

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Section: Curcumin and Liver Damagementioning

confidence: 99%

NF‐κB in liver diseases: a target for drug therapy

Muriel

2008

J of Applied Toxicology

148

106

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“…Minor metabolites of retinoic acid (RA), 9-cis RA and 9, 13-di-cis RA can stimulate the activation of latent TGF-β1 implying a direct link to fibrogenesis (68). Activated HSCs have increased expression of cell membrane receptors including integrins and receptor tyrosine kinases (RTKs) (69). Increased cytokine effects and remodeling of ECM perpetuate the activation of HSCs (70).…”

Section: Perpetuation Of Hsc Activationmentioning

confidence: 99%

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Houssein

Mahato

2007

Oligonucleotides

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Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of α1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed.

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“…When HSCs are activated, they show an increased capacity for proliferation, mobility, contractility, and synthesis of collagen and other components of the extracellular matrix (ECM) (Pinzani et al., 1998;Pinzani and Marra, 2001;Brandão et al, 2006). Excessive deposition of ECM is a characteristic of fibrogenesis, which effectively amplifies the fibrogenic response (Hui and Friedman, 2003;Parsons et al, 2007).…”

Section: Effects Of Hbx On Hscsmentioning

confidence: 99%

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1

Chen

Huang

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We investigated the effects of the hepatitis B virus X gene (HBV X) on the activation of human hepatic stellate cells (HSCs) and the possible mechanisms underlying the pathway. Recombinant plasmid pHBV-X-IRES2-EGFP was constructed and transfected into HL-7702 cells using a lipid-mediated method. Transfected cells were screened by G418, which detected stable expression of the X gene by reverse transcription (RT)-PCR and Western blot analysis, and named L02/x. Cells not subjected to G418-selection were analyzed to confirm the transient expression of the X gene and named L02/48x. Subsequently, L02/x and L02/48x, together with non-HBx-expressing cells, were cocultured with HSCs in a non-contact transwell system. After 36 h of co-culture, the proliferation and migration of HSCs was detected using different cell counting methods. Finally, the mRNA and protein levels of α-SMA, Col I, and TGFβ1 in HSCs were detected by real-time PCR and western blot analysis. RT-PCR and Western blot analysis showed that L02/x and L02/48x cells can express HBV X gene mRNA and protein. Additionally, HSCs co-cultured with L02/x or L02/48x cells showed significantly higher proliferation and migration levels than

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Signal transduction in hepatic stellate cells

Cited by 218 publications

References 69 publications

NF‐κB in liver diseases: a target for drug therapy

NF‐κB in liver diseases: a target for drug therapy

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1

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