Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl ameliorates porcine serum-induced immune liver fibrosis by inhibiting NF-κB signaling pathway and suppressing HSC activation

Bai, Facheng; Huang, Quanfang; Wei, Jinbin; Lv, Shujuan; Chen, Yuxin; Liang, Chunhong; Wei, Ling; Lu, Zhaojun; Lin, Xiaobo

doi:10.1016/j.intimp.2017.10.028

Cited by 21 publications

(17 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cell migration was determined by wound healing assay 10 . HSC‐T6 cells were cultured in 6‐well plates (1 × 10 5 cells/well) for 24 hours to form a monolayer, which was scratched using a small plastic comb to generate a linear wound.…”

Section: Methodsmentioning

confidence: 99%

“…When cells are stimulated, IκB kinase (IKK) phosphorylates and subsequently degrades the IκBα protein, leading to translocation of the NF‐κB heterodimer into the nucleus and then inducing the expression of inflammatory genes 9 . It has been reported that inhibiting the NF‐κB signalling pathway can ameliorate the severity of liver fibrosis 10 . Thus, the NF‐κB signalling pathway is also an attractive target for the treatment of hepatic fibrosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retracted: Tormentic acid inhibits hepatic stellate cells activation via blocking PI3K/Akt/mTOR and NF‐κB signalling pathways

Lin

Wei

et al. 2020

Cell Biochemistry & Function

Self Cite

View full text Add to dashboard Cite

The present study was to investigate the inhibitory effect and underlying mechanism of Tormentic acid (TA) on hepatic stellate cells (HSCs). HSC‐T6 cells were stimulated with Platelet‐derived growth factor‐BB (PDGF‐BB) and TA, and then cell proliferation, apoptosis, inflammatory factor, and collagen‐related indicators were detected. In order to elucidate the potential mechanism, the PI3K/Akt/mTOR and NF‐κB signalling pathways were also detected. The results showed that TA treatment markedly inhibited PDGF‐BB‐stimulated HSC‐T6 cell activation, as evidenced by the inhibition of cell proliferation, migration and colony formation, as well as the decreased expression of TGF‐β and α‐SMA. TA treatment caused a significant increase in the activity of lactate dehydrogenase and significantly promoted cell apoptosis. TA treatment significantly reduced aspartate aminotransferase, alanine aminotransferase and total bilirubin activity. Importantly, TA inhibited the expression of collagen type I and III, alleviating the excessive deposition of extracellular matrix (ECM). Further experiments showed that TA administration significantly inhibited the phosphorylation of PI3K, Akt, FAK and mTOR and the protein expression of P70S6K, indicating the inhibition of the PI3K/Akt/mTOR pathway. Moreover, treatment with TA markedly decreased the phosphorylation of IκBα, NF‐κB p65 and IKKα/β, thereby blocking the NF‐κB signal transduction. In summary, this study demonstrates that TA significantly inhibits HSC activation and promotes cell apoptosis via the inhibition of the PI3K/Akt/mTOR and NF‐κB signalling pathways. Significance of the study Tormentic acid (TA) could inhibit HSC activation and alleviate collagen‐based ECM deposition, suggesting that TA exerted anti‐hepatic fibrosis. Further mechanism research revealed that the inhibition of TA on HSC activation might be through blocking the PI3K/Akt/mTOR and NF‐κB signalling pathways. These findings provided a new cue to understand the protective effect of TA against liver fibrosis, which may provide a potential nature medicine for the treatment of liver fibrosis.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retracted: Tormentic acid inhibits hepatic stellate cells activation via blocking PI3K/Akt/mTOR and NF‐κB signalling pathways

Lin

Wei

et al. 2020

Cell Biochemistry & Function

Self Cite

View full text Add to dashboard Cite

show abstract

“…Different models of hepatic fibrosis have been used to study the molecular pathogenesis of this disease. The PSinduced liver fibrosis model in rats manifests changes that are similar to those found in liver diseases in humans 13 . The current study demonstrated that both β-arrestin2, TGF-β1 and collagen were increased during fibrosis development in this model.…”

Section: Discussionsupporting

confidence: 59%

β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix

Sun

et al. 2020

Cell Death Dis

View full text Add to dashboard Cite

Hepatic fibrosis is a disease of the wound-healing response following chronic liver injury, and activated hepatic stellate cells (HSCs) play a crucial role in the progression of hepatic fibrosis. β-arrestin2 functions as a multiprotein scaffold to coordinate complex signal transduction networks. Although β-arrestin2 transduces diverse signals in cells, little is known about its involvement in the regulation of liver fibrosis. Our current study utilized a porcine serum-induced liver fibrosis model and found increased expression of β-arrestin2 in hepatic tissues with the progression of hepatic fibrosis, which was positively correlated with collagen levels. Furthermore, changes in human fibrotic samples were also observed. We next used β-arrestin2 −/− mice to demonstrate that β-arrestin2 deficiency ameliorates CCl 4-induced liver fibrosis and decreases collagen deposition. The in vitro depletion and overexpression experiments showed that decreased β-arrestin2 inhibited HSCs collagen production and elevated TβRIII expression, thus downregulating the TGF-β1 pathway components Smad2, Smad3 and Akt. These findings suggest that β-arrestin2 deficiency ameliorates liver fibrosis in mice, and β-arrestin2 may be a potential treatment target in hepatic fibrosis.

show abstract

“…This finding demonstrated that NF-κB serves as a link between oxidative/nitrative stress and immune damage and illustrated the complexity of CYP2E1 transcriptional regulation [20]. In alcohol-induced liver injury, the increased expression and metabolic activity of CYP2E1 as well as the increased oxidative metabolism could generate substantial amounts of reactive oxygen free radicals that induce lipid peroxidation, which could damage the structures and functions of various organelles and enzymes, suppress proteasome activity, decrease acetaldehyde adduct proteolysis, and damage liver cells [21,22]. Inimmune-mediated liver injury, CYP2E1 was downregulated, and CYP2E1-catalyzed oxidative metabolism was weakened.…”

Section: Discussionmentioning

confidence: 99%

NF-κB-mediated regulation of rat CYP2E1 by two independent signaling pathways

Kang

et al. 2019

PLoS ONE

View full text Add to dashboard Cite

Cytochrome P450 2E1 (CYP2E1) plays an important role in both alcohol-induced and immune-mediated liver injury. However, the mechanism underlying CYP2E1 transcriptional regulation has not been clarified. This study focused on the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways in alcohol-induced and immune-mediated liver injury rat models. Male Sprague-Dawley rats were used in pharmacokinetic, molecular pharmacology, and morphology experiments. A rat model of alcohol-induced liver injury (AL) was established by feeding an ethanol-containing diet (42 g/kg/day) for 5 weeks as indicated. A rat immune-mediated liver injury (IM) model was established by the sequential injection of bacillus Calmette-Guérin (BCG, 125 mg/kg, once) via the tail vein after test day 21 and 10 μg/kg LPS 13 days later. HPLC, real-time PCR, western blot and ELISA analyses were performed. CYP2E1 expression was enhanced during the process of alcohol-induced liver injury (increased by 56%, P < 0.05) and significantly reduced during that of immune-mediated liver injury (reducedby52%, P < 0.05). NF-κB was activated in both the AL and IM groups (increased by 56% and76%, respectively, P < 0.05). Compared to those in the livers of AL model rats, the interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and iNOS levels in IM model rat livers were increased (increased by 26%, 21% and 101%, respectively, P < 0.05). The differential changes in CYP2E1 in the processes of alcohol-induced and immune-mediated liver injury may result from the differential expression of inflammatory cytokines and iNOS after NF-κB activation, leading to the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways.

show abstract

Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl ameliorates porcine serum-induced immune liver fibrosis by inhibiting NF-κB signaling pathway and suppressing HSC activation

Cited by 21 publications

References 23 publications

Retracted: Tormentic acid inhibits hepatic stellate cells activation via blocking PI3K/Akt/mTOR and NF‐κB signalling pathways

Retracted: Tormentic acid inhibits hepatic stellate cells activation via blocking PI3K/Akt/mTOR and NF‐κB signalling pathways

β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix

NF-κB-mediated regulation of rat CYP2E1 by two independent signaling pathways

Contact Info

Product

Resources

About