Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis

Li, Juan; Zhao, Yingren; Tian, Zhen

doi:10.4254/wjh.v11.i5.412

Cited by 40 publications

(29 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have shown that liver injury caused by different factors has relatively specific inflammatory microenvironment characteristics 22,23 . We found that TNF-α was significantly increased in the livers of WT rats after LPS injection.…”

Section: Discussionmentioning

confidence: 99%

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

et al. 2020

View full text Add to dashboard Cite

Previous studies have shown that tumor necrosis factor (TNF)-α is a mediator of hepatotoxicity in liver injury. Moreover, TNF-α has also been reported to have a protective effect in liver regeneration, yet the function of TNF-α during liver injury remains controversial. Here, we report that the concentration of TNF-α determines its functions. High concentrations of TNF-α could aggravate LPS-induced liver injury. However, the TNF-α level was unchanged during APAP-induced liver injury, which exerted a protective effect. We expected that the concentration of TNF-α may affect its function. To test this hypothesis, TNF-α −/− rats or hepatocyte cells were treated with different concentrations of TNF-α. We found low TNF-α could reduce the levels of ALT and AST in the plasma of TNF-α −/− rats and promote the proliferation of hepatocyte cells. However, the levels of ALT and AST increased gradually with increasing TNF-α concentration after reaching the lowest value. Moreover, we showed that TNF-α affects the cell proliferation and cell death of hepatocytes by regulating Yap activity. Low TNF-α promoted Yap1 nuclear translocation, triggering the proliferation of hepatocytes. However, high TNF-α triggered the phosphorylation and inactivation of Yap1, preventing its nuclear import and consequently promoting cell death. Collectively, our findings provide novel evidence that the concentration of TNF-α is an important factor affecting its function in liver injury, which may provide a reference for the clinical treatment of liver injury.

show abstract

Section: Discussionmentioning

confidence: 99%

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

et al. 2020

View full text Add to dashboard Cite

show abstract

“…For instance, KCs can respond to exposure to LPS by binding to TLR4 which leads to production of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12, IL-18, etc.) and other chemokines [72], most of them being actively involved in HSCs activation (Table 2) [5,[73][74][75]. Other macrophages recruited to the liver in the case of inflammation, are also involved in secretion of pro-and anti-inflammatory cytokines, depending on their type (proinflammatory M1 or immunosuppressive M2, respectively).…”

Section: Inflammatory Signals From Kupffer Cells and Other Inflammatimentioning

confidence: 99%

Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development

Ignat

Dinescu

Costache

2020

Cells

View full text Add to dashboard Cite

Inflammation has been known to be an important driver of fibrogenesis in the liver and onset of hepatic fibrosis. It starts off as a process meant to protect the liver from further damage, but it can become the main promoter of liver fibrosis. There are many inflammation-related pathways activated during liver fibrosis that lead to hepatic stellate cells (HSCs) activation and collagen-deposition in the liver. Such events are mostly modulated upstream of HSCs and involve signals from hepatocytes and innate immune cells. One particular event is represented by cell death during liver injury that generates multiple inflammatory signals that further trigger sterile inflammation and enhancement of inflammatory response. The assembly of inflammasome that responds to danger-associated molecular patterns (DAMPs) stimulates the release of pro-inflammatory cytokines and at the same time, initiates programmed cell death called pyroptosis. This review focuses on cellular and molecular mechanisms responsible for initiation and progress of inflammation in the liver.

show abstract

“…Its 1-year mortality ranges from 1% to 57% depending on the stage. To date, the only treatment of developed cirrhosis is liver transplantation [1].…”

Section: Introductionmentioning

confidence: 99%

Water-Soluble Pristine C₆₀ Fullerenes Inhibit Liver Fibrotic Alteration and Prevent Liver Cirrhosis in Rats

Kuznietsova

Dziubenko

Hurmach

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Liver cirrhosis is an outcome of a wide range of liver chronic diseases. It is attributed to oxidative stress; therefore, antioxidant usage could be a promising treatment of that. So, exploring the impact of effective free radical scavenger pristine C60 fullerenes on liver fibrosis and cirrhosis and their ability to interact with main growth factor receptors involved in liver fibrogenesis was aimed to be discovered. We used N-diethylnitrosamine/carbon tetrachloride-induced simulations of rat liver fibrosis (10 weeks) and cirrhosis (15 weeks). Pristine C60 fullerene aqueous colloid solution (C60FAS) was injected daily at a dose of 0.25 mg/kg throughout the experiment. Liver morphology and functional and redox states were assessed. C60 fullerenes’ ability to interact with epidermal, vasoendothelial, platelet-derived, and fibroblast growth factor receptors (EGFR, VEGFR, PDGFR, and FGFR, respectively) was estimated by computational modeling. We observed that C60FAS reduced the severity of fibrosis in fibrotic rats (0.75 vs. 3.0 points according to Ishak score), attenuated the hepatocyte injury, normalized elevated blood serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and mitigated oxidative stress manifestation in liver tissue restoring its redox balance. When applied to cirrhotic animals, C60FAS reduced connective tissue deposition as well (2.4 vs. 5.4 points according to Ishak score), diminished ALP and LDH (by 16% and 61%), and normalized conjugated and nonconjugated bilirubin, restoring the liver function. Altered liver lipid and protein peroxides and glutathione peroxidase activity were also leveled. Within a computer simulation, it was shown that C60 fullerenes can block hinge prohibiting ATP binding for EGFR and FGFR and thus blocking associated signal pathways. This ability in addition to their antioxidant properties may contribute to C60 fullerene’s antifibrotic action. Thus, C60FAS may have a substantial therapeutic potential as an inhibitor of liver fibrosis and cirrhosis.

show abstract

Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis

Cited by 40 publications

References 52 publications

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development

Water-Soluble Pristine C₆₀ Fullerenes Inhibit Liver Fibrotic Alteration and Prevent Liver Cirrhosis in Rats

Contact Info

Product

Resources

About

Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis

Cited by 40 publications

References 52 publications

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development

Water-Soluble Pristine C60 Fullerenes Inhibit Liver Fibrotic Alteration and Prevent Liver Cirrhosis in Rats

Contact Info

Product

Resources

About

Water-Soluble Pristine C₆₀ Fullerenes Inhibit Liver Fibrotic Alteration and Prevent Liver Cirrhosis in Rats