Effects of rhubarb on migration of rat hepatic stellate cells

Lin, Yun‐Lian; Wu, Chenguang; Huang, Yi-Tsau

doi:10.1111/j.1440-1746.2008.05573.x

Cited by 21 publications

(12 citation statements)

References 41 publications

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“…Second, ligation of HMGB1 to TLR4 can also activate other intracellular signal pathways besides JNK and PI3K/Akt signal pathway. For instance, MAPK / ERK signaling is involved in the HSCs proliferation and TGF-β1 can mediate the migration of HSCs possibly by Smad2/3 phosphorylation and MAPK pathway [47], [48]. Novo et al showed that mitochondrial-dependent ROS-mediated activation of ERK and JNK participated in hypoxia-induced migration of HSCs [49].…”

Section: Discussionmentioning

confidence: 99%

High Mobility Group Box-1 Promotes the Proliferation and Migration of Hepatic Stellate Cells via TLR4-Dependent Signal Pathways of PI3K/Akt and JNK

Wang

et al. 2013

PLoS ONE

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BackgroundThe migration of hepatic stellate cells (HSCs) is essential to the hepatic fibrotic response, and recently High-mobility group box 1 (HMGB1) has been shown up-regulated during liver fibrosis. Nevertheless, whether HMGB1 can modulate the proliferation and migration of HSCs is poorly understood, as well as the involved intracellular signaling. In this study, we examined the effect of HMGB1 on proliferation, migration, pro-fibrotic function of HSCs and investigated whether toll-like family of receptor 4 (TLR4) dependent signal pathway is involved in the intracellular signaling regulation.Methodology/Principal FindingsModified transwell chamber system to mimic the space of Disse was used to evaluate the migration of human primary HSCs, and the protein expressions of related signal factors were evaluated by western blot. Cell proliferation was analyzed by MTT assay, the pro-fibrotic functions of HSCs by qRT-PCR and ELISA respectively. Recombinant human HMGB1 could significantly promote migration of HSCs under both haptotactic and chemotactic stimulation, especially the latter. Human TLR4 neutralizing antibody could markedly inhibit HMGB1-induced migration of HSCs. HMGB1 could enhance the phosphorylation of JNK and PI3K/Akt, and TLR4 neutralizing antibody inhibited HMGB1-enhanced phosphorylation of JNK and PI3K/Akt and activation of NF-κB. JNK inhibitor (SP600125) and PI3K inhibitor (LY 294002) significantly inhibited HMGB1-induced proliferation and migration of HSCs, and also reduced HMGB1-enhanced related collagen expressions and pro-fibrotic cytokines production.Conclusions/SignificanceHMGB1 could significantly enhance migration of HSCs in vitro, and TLR4-dependent JNK and PI3K/Akt signal pathways are involved in the HMGB1-induced proliferation, migration and pro-fibrotic effects of HSCs, which indicates HMGB1 might be an effective target to treat liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

High Mobility Group Box-1 Promotes the Proliferation and Migration of Hepatic Stellate Cells via TLR4-Dependent Signal Pathways of PI3K/Akt and JNK

Wang

et al. 2013

PLoS ONE

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“…The result indicated that p-P38 and p-JNK were significantly elevated 30 min and 2 h after TGF-β treatment; this was consistent with the previous study. 41 However, we did not observe the elevation of p-ERK. We treated the HSCs with various concentrations of TGP (1−8 μg/mL) or propolin G (1−8 μM) prior to treatment with TGF-β for 15 min.…”

Section: ■ Results and Discussionmentioning

confidence: 82%

Taiwanese Green Propolis and Propolin G Protect the Liver from the Pathogenesis of Fibrosis via Eliminating TGF-β-Induced Smad2/3 Phosphorylation

Hsieh

Chen

et al. 2014

J. Agric. Food Chem.

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Pathogenesis of fibrosis is a common process leading to chronic liver diseases and liver cirrhosis. New compounds for disease treatment and adjuvant therapy have been important issues in recent years. In this study, we isolated propolin G from Taiwanese green propolis (TGP) and investigated its antifibrotic effects by utilizing active hepatic stellate cells (HSCs) fibrosis model. Our results showed that TGP and propolin G inhibited α-SMA, collagen expression, and proliferation of HSC-T6 cells after TGF-β treatment. They also reduced the accumulation of extracellular matrix (ECM) components such as collagen Iα1 (Col Iα1) through down-regulating JNK signaling. Subsequently, mRNA and protein expression of Smad2/3 but no other Smad members was specifically down-regulated in the presence of propolin G. This effect also significantly induced apoptosis-associated expression of cleaved caspase-3 and caspase-7 proteins for fibrotic cell clearance. In in vivo experiments, we found that propolin G and TGP can reduce plasma alanine aminotransferase (ALT) activation and perhaps lead to the prevention of alcohol-induced liver cirrhosis. Furthermore, TGP can significantly decrease the malondialdehyde (MDA) level but has no influence on plasma or hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, suggesting TGP protects the liver from alcohol-induced injury through antioxidant-independent pathways. In conclusion, this study provides a new perspective of propolin G and TGP on liver protection, and its application has potential for health management by daily supplement or adjuvant therapy in related diseases.

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“…The bottom wells were filled with serum-free medium co-treating with LPS plus Tan IIA (10 µM) or Sal B (200 µM) for 24 hr, and the entire chamber was incubated at 37°C for 24 hr. Cells migrated to the lower surface of the membrane were stained with hematoxylin (Sigma-Aldrich) to define the cell nuclei, as previously reported by us [32].…”

Section: Methodsmentioning

confidence: 99%

Inhibitory Effect of Tanshinone IIA on Rat Hepatic Stellate Cells

Liu¹,

Huang

2014

PLoS ONE

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BackgroundAnti-inflammation via inhibition of NF-κB pathways in hepatic stellate cells (HSCs) is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C19H18O3, Tan IIA) is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.Materials and MethodsThe cell line of rat hepatic stellate cells (HSC-T6) was stimulated with lipopolysaccharide (LPS) (100 ng/ml). Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with Tan IIA (1, 3 and 10 µM), then induced by LPS (100 ng/ml). NF-κB activity was evaluated by the luciferase reporter gene assay. Western blotting analysis was performed to measure NF-κB-p65, and phosphorylations of MAPKs (ERK, JNK, p38). Cell chemotaxis was assessed by both wound-healing assay and trans-well invasion assay. Quantitative real-time PCR was used to detect gene expression in HSC-T6 cells.ResultsAll concentrations of drugs showed no cytotoxicity against HSC-T6 cells. LPS stimulated NF-κB luciferase activities, nuclear translocation of NF-κB-p65, and phosphorylations of ERK, JNK and p38, all of which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1β, TNF-α, IL-6, ICAM-1, iNOS, and α-SMA in HSC-T6 cells.ConclusionOur results demonstrated that Tan IIA decreased LPS-induced HSC activation.

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Effects of rhubarb on migration of rat hepatic stellate cells

Abstract: The results suggest that rhubarb attenuated TGF-beta1-mediated migration of HSCs possibly by interfering with Smad2/3 phosphorylation, the MAPK pathway, and MMP-2 activity.

Cited by 21 publications

References 41 publications

High Mobility Group Box-1 Promotes the Proliferation and Migration of Hepatic Stellate Cells via TLR4-Dependent Signal Pathways of PI3K/Akt and JNK

High Mobility Group Box-1 Promotes the Proliferation and Migration of Hepatic Stellate Cells via TLR4-Dependent Signal Pathways of PI3K/Akt and JNK

Taiwanese Green Propolis and Propolin G Protect the Liver from the Pathogenesis of Fibrosis via Eliminating TGF-β-Induced Smad2/3 Phosphorylation

Inhibitory Effect of Tanshinone IIA on Rat Hepatic Stellate Cells

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