Pathogenesis of liver cirrhosis

Zhou, Wence; Zhang, Quanbao; Qiao, Liang

doi:10.3748/wjg.v20.i23.7312

Cited by 480 publications

(458 citation statements)

References 189 publications

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“…It is thought that fibrosis is a natural wound healing response that goes awry in the setting of persistent tissue injury. As fibrosis becomes more severe, it may have multiple negative effects in the liver, including obstruction of biliary canaliculi, venous congestion, and support of a proinflammatory milieu through HSC‐mediated secretion of inflammatory signaling molecules 41. These processes may exacerbate the effects from ongoing hepatic insults, contributing to progressive liver failure.…”

Section: Discussionmentioning

confidence: 99%

Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP‐305, a novel farnesoid X receptor agonist

Erstad

Farrar

Ghoshal

et al. 2018

Hepatology Communications

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We examined a novel farnesoid X receptor agonist, EDP‐305, for its antifibrotic effect in bile duct ligation (BDL) and choline‐deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) models of hepatic injury. We used molecular magnetic resonance imaging with the type 1 collagen‐binding probe EP‐3533 and the oxidized collagen‐specific probe gadolinium hydrazide to noninvasively measure treatment response. BDL rats (n = 8 for each group) were treated with either low or high doses of EDP‐305 starting on day 4 after BDL and were imaged on day 18. CDAHFD mice (n = 8 for each group) were treated starting at 6 weeks after the diet and were imaged at 12 weeks. Liver tissue was subjected to pathologic and morphometric scoring of fibrosis, hydroxyproline quantitation, and determination of fibrogenic messenger RNA expression. High‐dose EDP‐305 (30 mg/kg) reduced liver fibrosis in both the BDL and CDAHFD models as measured by collagen proportional area, hydroxyproline analysis, and fibrogenic gene expression (all P < 0.05). Magnetic resonance signal intensity with both EP‐3533 in the BDL model and gadolinium hydrazide in the CDAHFD model was reduced with EDP‐305 30 mg/kg treatment (P < 0.01). Histologically, EDP‐305 30 mg/kg halted fibrosis progression in the CDAHFD model. Conclusion: EDP‐305 reduced fibrosis progression in rat BDL and mouse CDAHFD models. Molecular imaging of collagen and oxidized collagen is sensitive to changes in fibrosis and could be used to noninvasively measure treatment response in clinical trials. (Hepatology Communications 2018;2:821‐835)

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Section: Discussionmentioning

confidence: 99%

Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP‐305, a novel farnesoid X receptor agonist

Erstad

Farrar

Ghoshal

et al. 2018

Hepatology Communications

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“…It is initially a critical intermediary step in the progression to liver cirrhosis and latterly hepatocellular carcinoma (Zhou et al, 2014). In hepatic fibrosis, hepatic stellate cells are activated and form an excessive extra-cellular matrix that includes collagens and fibronectins (Tsukada et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of methanolic extract of Phragmites karka on carbon tetrachloride-induced liver fibrosis in rat

Rehman

Liaqat

Asghar

et al. 2017

Bangladesh J Pharmacol

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Phragmites karka has been reported for its anti-inflammatory and analgesic activities. Here, extracts of leaf and rhizome of the plant were individually investigated in CCl4-induced hepatofibrosis in male Wistar rats by administering CCl4 intraperitoneally biweekly for 6 weeks. Afterwards the animals were investigated for liver fibrosis at biochemical, molecular and histological levels, and it showed a profound increase (p<0.001) in elevation of serum levels of transaminases, γ-glutamyl transpeptidase, mRNA expression of α smooth muscle actin, collagen and transforming growth factor beta (TGFβ), and extracellular matrix deposition and perilobular necrosis. Both extracts markedly (p<0.001) decreased the elevated levels of these markers. Histopathological investigations also substantiated the above results by exhibiting a decreased in extracellular matrix deposition in post-treatment animals. In conclusion, both extracts had substantially modified the biochemical and molecular markers of liver fibrosis, in addition to histological improvement in architecture of liver.

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“…Liver cirrhosis (LC), a chronic liver disease of progression and diffusivity, is usually caused by viral hepatitis, longterm excessive drinking, long-term cholestasis, chemical toxin or drugs, liver congestion, parasitosis, genetic and metabolic diseases, etc., which are able to trigger the following processes: apoptosis and compensatory regeneration of hepatocytes (Zhou et al, 2014). Moreover, the sustained liver damages induced by the above-mentioned factors can activate hepatic stellate cells (HSCs), and then result in over abundant synthesis and insufficient degradation of collagens (Pereira et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Tumor necrosis factor alpha (TNFα) and transforming growth factor beta (TGFβ) could stimulate activation of HSCs, which are known to be activated as the predominant cells responsible for liver fibrosis. Furthermore, interleukins (ILs) were shown to have complicated effects on immune response, inflammation, and liver fibrogenesis (Zhou et al, 2014). Chou et al (2006) demonstrated that IL-10 inhibited fibrogenic and pro-inflammatory gene responses in CCl 4 -induced mice, and Zhang et al (2007) showed that IL-10 presented an anti-fibrogenic effect by down-regulating the activity of HSCs.…”

Section: Introductionmentioning

confidence: 99%

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

Wang¹,

Zhao²,

Chen³

et al. 2017

Afr. J. Biotechnol.

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Liver cirrhosis (LC) is a kind of liver disease which is pathologically characterized by abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. To explore the mechanism of LC occurrence at the level of mRNA, Rat Genome 230 2.0 Array was used to detect gene expression profiles of rat fibrotic livers in 3, 6 and 9 weeks after CCl 4 treatment in this study. It was found that a total of 305 genes including 153 up-regulated, 150 down-regulated and 2 up/down-regulated genes, were related to LC occurrence. Then, k-means clustering was employed to classify above 305 genes into 5 clusters based on gene expression similarity, and EASE analysis further indicated that the above genes were mainly associated with metabolic process, stress reaction, cell growth and apoptosis/death. Thereafter, ingenuity pathway analysis (IPA) software was used to analyze potential effects of the above-mentioned 305 genes, and the results suggested that lipid metabolism and cell growth were inhibited while cell apoptosis/death was activated, but immune/inflammatory response was first activated and then inhibited. Furthermore, IPA also predicted that several signal pathways "ERK/MAPK Signaling", "p38 MAPK", "Endothelin-1 Signaling", "Growth Hormone Signaling", "LPS/IL-1-mediated inhibition of RXR function" and "IL-6 Signaling" were involved in regulating the occurrence of liver cirrhosis. It was concluded that 305 genes and 3 kinds of physiological activities were closely related to LC occurrence.

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Pathogenesis of liver cirrhosis

Cited by 480 publications

References 189 publications

Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP‐305, a novel farnesoid X receptor agonist

Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP‐305, a novel farnesoid X receptor agonist

Evaluation of methanolic extract of Phragmites karka on carbon tetrachloride-induced liver fibrosis in rat

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

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