scholarly journals Regulation of activation and proliferation of hepatic stellate cells through the Wnt signaling pathway: Implications for treatment of liver fibrosis

2014 ◽  
Vol 22 (21) ◽  
pp. 3048
Author(s):  
Zhi-Gang Ma ◽  
Lan Chen ◽  
Ling-Ling Zhan ◽  
Xiao-Ping Lv
Keyword(s):  
Liver Fibrosis ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Hepatic Stellate Cells ◽  
Wnt Signaling Pathway ◽  
Stellate Cells

scholarly journals MiR-571 affects the development and progression of liver fibrosis by regulating the Notch3 pathway

2021 ◽  
Author(s):  
Shuo Cong ◽  
Yongmei Liu ◽  
Yi Li ◽  
Yu Chen ◽  
Rui Chen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Western Blot ◽  
Signaling Pathway ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Rt Pcr ◽  
Promote Cell Proliferation ◽  
Notch 3 ◽  
And Migration ◽  
Set Up

Abstract Exploring the expression of miR-571 in patients with liver fibrosis and its role in the progression of liver fibrosis. A total of 74 patients with chronic hepatitis and cirrhosis accompanied by liver fibrosis in our institution from September to December 2018 were collected for study, and the expression of miR-571 in patients with different progressions of liver fibrosis was determined by RT-PCR and Western blot analysis. Set up Notch3 up group and Notch3 down regulated group, RT-PCR and Western blot were used to determine the effect of Notch signaling on the expression of fibrogenic α-SMA, collagen I. CCK-8, cell scratch assays, Transwell assays, flow cytometry were used to determine the effect of miR-571 on LX-2 proliferation, migration, apoptosis in human stem stellate cells, and RT-PCR, Western blot assays were performed to determine the effect of miR-571 on the Notch3 signaling pathway and the expression of profibrogenic factors. miR-571 is up-regulated in patients with liver fibrosis and is associated with the progression of liver fibrosis. Notch3 signaling pathway can promote the expression of fibroblast in human hepatic stellate cells; miR-571 can inhibit the apoptosis of human hepatic stellate cells, promote cell proliferation and migration; up regulation of miR-571 can promote the expression of Notch3 and Jagged 1; up regulation of miR-571 can also promote the expression of fibroblast. miR-571 can promote the activation of human stem stellate cells and the expression of fibroblasts through Notch 3 signaling pathway.

scholarly journals Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options: An Update

2021 ◽  
Vol 000 (000) ◽  
pp. 000-000
Author(s):  
Kristina Duspara ◽  
Kristina Bojanic ◽  
Josipa Ivanusic Pejic ◽  
Lucija Kuna ◽  
Tea Omanovic Kolaric ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

scholarly journals Heme Oxygenase-1 Suppresses Wnt Signaling Pathway in Nonalcoholic Steatohepatitis-Related Liver Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jinghua Du ◽  
Weiguang Ren ◽  
Qingshan Zhang ◽  
Na Fu ◽  
Fang Han ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Heme Oxygenase ◽  
Nonalcoholic Steatohepatitis ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Heme Oxygenase 1 ◽  
Inflammatory Infiltration

Background and Aim. Heme oxygenase-1 (HO-1) has been verified to play an important role in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. In this study, we aimed to clarify whether induction of HO-1 reverses steatofibrosis via suppression of the Wnt signaling pathway and to explore the potential mechanism of HO-1 on NASH-related liver fibrosis. Methods. Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP. Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis. HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1. qPCR and Western blot were used to assess the mRNA and protein levels of genes. Results. MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections. Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST. We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a. The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study. Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies. Conclusion. Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis. Thus, these results may suggest a new therapeutic strategy for NASH-related 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 MiR-571 affects the development and progression of liver fibrosis by regulating the Notch3 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuo Cong ◽  
Yongmei Liu ◽  
Yi Li ◽  
Yu Chen ◽  
Rui Chen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Western Blot ◽  
Signaling Pathway ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Rt Pcr ◽  
Related Factors ◽  
Promote Cell Proliferation ◽  
And Migration ◽  
Set Up

AbstractExploring the expression of miR-571 in patients with liver fibrosis and its role in the progression of liver fibrosis. A total of 74 patients with liver fibrosis in our institution from September to December 2018 were collected for study, and the expression of miR-571, Notch3 and Jagged1 in patients with different progressions of liver fibrosis was determined by RT-PCR and Western blot analysis. Set up Notch3 up group and Notch3 down regulated group, RT-PCR and Western blot were used to determine the effect of Notch signaling on the expression of fibrogenic factors. CCK-8, cell scratch assays, Transwell assays, flow cytometry were used to determine the effect of miR-571 on LX-2 proliferation, migration, apoptosis in human stem stellate cells, and RT-PCR, Western blot assays were performed to determine the effect of miR-571 on the Notch3 signaling pathway and the expression of profibrogenic factors. miR-571, Notch3 and Jagged1 are up-regulated in patients with liver fibrosis and is associated with the progression of liver fibrosis. Notch3 signaling pathway can promote the expression of fibroblast in human hepatic stellate cells; miR-571 can inhibit the apoptosis of human hepatic stellate cells, promote cell proliferation and migration; up regulation of miR-571 can promote the expression of Notch3 and Jagged1, and up-regulation of miR-571 also promoted the expression of related fibroblasts. MiR-571 can promote the activation of human stem cell stellate cells and the expression of fibroblast related factors through Notch3 signaling pathway.

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