scholarly journals Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 2041
Author(s):  
Ji Hye Yang ◽  
Sae Kwang Ku ◽  
IL Je Cho ◽  
Je Hyeon Lee ◽  
Chang-Su Na ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Inflammatory Responses ◽  
Chronic Liver ◽  
Mrna Levels ◽  
Chronic Liver Injury ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl4)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl4-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.

scholarly journals Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro

2016 ◽  
Vol 40 (1-2) ◽  
pp. 49-61 ◽  
Author(s):  
Quanfang Huang ◽  
Chunhong Liang ◽  
Ling Wei ◽  
Jinlan Nie ◽  
Shengjuan Lu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Inhibitory Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitory Protein ◽  
Liver Tissues

Background/Aims: Raf kinase inhibitory protein (RKIP) is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear. Methods: In the present study, hepatic fibrosis was induced by porcine serum (PS) in rats and primary hepatic stellate cells (HSCs) were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression. Results: RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways. Conclusion: Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.

scholarly journals Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells

2021 ◽  
Vol 22 (24) ◽  
pp. 13354
Author(s):  
Seita Kataoka ◽  
Atsushi Umemura ◽  
Keiichiro Okuda ◽  
Hiroyoshi Taketani ◽  
Yuya Seko ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl4). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-β (TGF-β1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl4-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-β1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-β1/SMAD signaling and autophagy in HSCs.

scholarly journals Astragaloside Inhibits Hepatic Fibrosis by Modulation of TGF-β1/Smad Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Xingxing Yuan ◽  
Zhiqiang Gong ◽  
Bingyu Wang ◽  
Xueying Guo ◽  
Lei Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Collagen Fibers ◽  
Control Group ◽  
Smad Signaling ◽  
Smad Proteins ◽  
Smad Signaling Pathway ◽  
Smad 3

Activation of HSC is a pivotal step in hepatic fibrosis. In the activation of HSC, the TGF-β1 plays a key role that can promote the occurrence of hepatic fibrosis by combining with Smad proteins. Astragaloside is the main active component extracted from Radix Astragali that has the effect of antioxidation and hepatoprotection. In the present study, we investigated the mechanism of astragalosides inhibiting hepatic fibrosis in vitro and in vivo. In vitro, astragalosides inhibited the activation of HSC and regulated the expression of MMP-2 and TIMP-2 and reduced the formation of collagen fibers. In vivo, administration of astragalosides decreased the serum ALT, AST, and TBiL in rats by reducing oxidative stress. Astragalosides also attenuated hepatic fibrosis by reducing the concentration of hydroxyproline and inhibiting the formation of collagen fibers. The expressions of TGF-β1, TβR-I, p-Smad 2, and p-Smad 3 were downregulated after astragalosides treatments, while Smad 7 was upregulated compared to the control group. The results indicated that the effect of astragaloside on hepatic fibrosis was related to the inhibition of HSC activation and the modulation of the TGF-β1/Smad signaling pathway.

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

2019 ◽  
Vol 35 (4) ◽  
pp. 419-429 ◽  
Author(s):  
Qiong Zhang ◽  
Xuhong Chang ◽  
Haibing Wang ◽  
Yunlan Liu ◽  
Xiaoxia Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

scholarly journals Periplaneta Americana Extract may Attenuate 2,4,6-Trinitrobenzenesulfonic Acid-Induced Intestinal Fibrosis by Inhibiting TGF-β/Smad Signaling Pathway

2021 ◽  
Author(s):  
Jing Liu ◽  
Pin Lv ◽  
Xiang Rao ◽  
Jiajia Wang
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Periplaneta Americana ◽  
Collagen I ◽  
Smad Signaling ◽  
Intestinal Fibrosis ◽  
Smad Signaling Pathway

Abstract PurposeIntestinal fibrosis is an incurable digestive disease accompanied by stricture formation, and it has an increasing incidence in recent years. Periplaneta americana is one of the medicinal insects with a long history. There are few reports on the effect of intestinal fibrosis. This study aims to evaluate the inhibitory effect of PA treatment on intestinal fibrosis. MethodsTNBS was used to establish intestinal fibrosis model by enema in BALB/c mice. The mice were treated with PA (50, 100, 200 mg/kg body weight) and 5-aminosalicylic acid (5-ASA) (40mg/kg) by gavage once a day for 6 weeks. At the end of the last week, the mice were sacrificed. Colon samples were collected for H&E and Masson staining. The mRNA and protein expression of α-smooth muscle actin (α-SMA), collagen I and the transforming growth factor-β (TGF-β) / Smad signaling pathway were conducted by real-time PCR and western blot analysis. In vitro, TGF-β1 was used to induce intestinal fibrosis at human colon fibroblasts (CCD-18Co). And using real-time PCR and western blot methods to detect the expression of α-SMA and collagen I. ResultsPA inhibited the expression of α-SMA and collagen I in vivo and in vitro. But the difference was that PA inhibited the TGF-β/Smad signaling pathway in vivo, and the same results had not been obtained in vitro. Conclusion: PA may attenuate intestinal fibrosis by inhibiting TGF-β/Smad signaling pathway, but more experiments were needed to prove it in vitro. ConclusionsPA has potential pharmacological effects in inhibiting intestinal fibrosis, and the TGF-β/Smad signaling pathway seemed promising.

701 HEPATIC STEATOSIS AND BACTERIAL TRANSLOCATION MODULATES PROGRESSION OF HEPATIC FIBROSIS DURING CHRONIC LIVER INJURY

2009 ◽  
Vol 50 ◽  
pp. S257
Author(s):  
S. De Minicis ◽  
C. Rychlicki ◽  
L. Trozzi ◽  
S. Saccomanno ◽  
C. Candelaresi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Steatosis ◽  
Hepatic Fibrosis ◽  
Bacterial Translocation ◽  
Chronic Liver ◽  
Chronic Liver Injury

scholarly journals Mycelium Polysaccharides from Termitomyces albuminosus Attenuate CCl4-Induced Chronic Liver Injury Via Inhibiting TGFβ1/Smad3 and NF-κB Signal Pathways

2019 ◽  
Vol 20 (19) ◽  
pp. 4872 ◽  
Author(s):  
Zhao ◽  
Li ◽  
Feng ◽  
Zhang ◽  
Yuan ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Molar Ratio ◽  
Gas Chromatography Mass Spectrometry ◽  
Signal Pathways ◽  
Chronic Liver Injury ◽  
Potential Health ◽  
Anti Inflammatory

A major fraction (MPT-W), eluted by deionized water, was extracted from mycelium polysaccharides of Termitomyces albuminosus (MPT), and its antioxidant, anti-fibrosis, and anti-inflammatory activities in CCl4-induced chronic liver injury mice, as well as preliminary characterizations, were evaluated. The results showed that MPT-W was a polysaccharide of α- and β-configurations containing xylose (Xyl), fucose (Fuc), mannose (Man), galactose (Gal), and glucose (Glc) with a molar ratio of 0.29:8.67:37.89:35.98:16.60 by gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared (FT-IR) spectroscopy. Its molecular weight (Mw), obtained by high-performance gel permeation chromatography (HPGPC), was 1.30 × 105 Da. The antioxidant assays in vitro showed that MPT-W displayed scavenging free-radical abilities. Based on the data of in vivo experiments, MPT-W could inhibit TGFβ1/Smad3 and NF-κB pathways; decrease the level and activity of cytochrome P4502E1 (CYP2E1), malonaldehyde (MDA) and serum enzyme; activate the HO-1/Nrf2 pathway; and increase antioxidant enzymes to protect the liver in CCl4-induced chronic liver injury mice. Therefore, MPT-W could be a potentially natural and functional resource contributing to antioxidant, hepatoprotective, and anti-inflammatory effects with potential health benefits.

scholarly journals The polysaccharides from Grifola frondosa attenuate CCl4-induced hepatic fibrosis in rats via the TGF-β/Smad signaling pathway

RSC Advances ◽  
2019 ◽  
Vol 9 (58) ◽  
pp. 33684-33692 ◽  
Author(s):  
Chao Li ◽  
Meng Meng ◽  
Mingzhu Guo ◽  
Mengyang Wang ◽  
Aining Ju ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Grifola Frondosa ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

The TGF-β1/Smad signaling pathway has been linked to hepatic fibrosis.

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