Moniliformediquinone as a potential therapeutic agent, inactivation of hepatic stellate cell and inhibition of liver fibrosis in vivo

The novel small molecule HJC0123 will inhibit STAT3 activation in human HSCs resulting in decreased fibrogenesis, unveiling a potential role for its use as a therapeutic agent for the treatment of liver fibrosis.

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Heat shock protein 47 effects on hepatic stellate cell-associated receptors in hepatic fibrosis of Schistosoma japonicum-infected mice

Biological Chemistry ◽

10.1515/hsz-2017-0177 ◽

2017 ◽

Vol 398 (12) ◽

pp. 1357-1366 ◽

Cited By ~ 3

Author(s):

Yumin Zhao ◽

Zhisheng Dang ◽

Shuo Xu ◽

Shigui Chong

Keyword(s):

Heat Shock ◽

Liver Fibrosis ◽

Heat Shock Protein ◽

Schistosoma Japonicum ◽

Mouse Models ◽

Hepatic Stellate Cell ◽

Stellate Cell ◽

Endothelin Receptor ◽

Heat Shock Protein 47

AbstractThe study aimed to explore the regulation of heat shock protein 47 (HSP47) on expressions of receptors associated with hepatic stellate cell (HSC) in liver fibrosis mouse models induced bySchistosoma japonicum(S. japonicum). Mouse fibroblasts (NIH/3T3) were transfected with HSP47 shRNA plasmid by lipofectamine transfection, and experimental fibrosis in HSCs was studied inS. japonicummouse models treated with HSP47 shRNAin vivo. HSP47 expression was assessed using Western blot and real-time PCR. Flow cytometry was adopted to determine the expression of cell membrane receptors. HSP47-shRNA could markedly down-regulate the expression of collagen (Col1a1 and Col3a1). The expressions of HSP47, endothelin receptor A (ETAR) and endothelin receptor B (ETBR) significantly increased in the liver tissue of infected mice. However, the expressions of ETAR and HSP47 and ETBR remarkably decreased after the administration of HSP47 shRNAin vitroandin vivo. ETAR and ETBR levels were found to be positively correlated with HSP47 expression. HSP47 might exert influence on liver fibrosis via the regulation of ETAR and ETBR.

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Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis

Gastroenterology ◽

10.1016/s0016-5085(99)70406-3 ◽

1999 ◽

Vol 117 (5) ◽

pp. 1198-1204 ◽

Cited By ~ 138

Author(s):

Jianliang Zhu ◽

Jian Wu ◽

Edward Frizell ◽

Shu-Ling Liu ◽

Reza Bashey ◽

...

Keyword(s):

Cell Proliferation ◽

Liver Fibrosis ◽

Hepatic Stellate Cell ◽

Stellate Cell ◽

In Vivo Model ◽

Proliferation In Vitro

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Snail1 transcription factor is a critical mediator of hepatic stellate cell activation following hepatic injury

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00141.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. G316-G326 ◽

Cited By ~ 17

Author(s):

Melania Scarpa ◽

Alessia R. Grillo ◽

Paola Brun ◽

Veronica Macchi ◽

Annalisa Stefani ◽

...

Keyword(s):

Wound Healing ◽

Transcription Factor ◽

Liver Fibrosis ◽

Liver Injury ◽

Mrna Expression ◽

Hepatic Stellate Cell ◽

Stellate Cell ◽

Qrt Pcr

Following liver injury, the wound-healing process is characterized by hepatic stellate cell (HSC) activation from the quiescent fat-storing phenotype to a highly proliferative myofibroblast-like phenotype. Snail1 is a transcription factor best known for its ability to trigger epithelial-mesenchymal transition, to influence mesoderm formation during embryonic development, and to favor cell survival. In this study, we evaluated the expression of Snail1 in experimental and human liver fibrosis and analyzed its role in the HSC transdifferentiation process. Liver samples from patients with liver fibrosis and from mice treated by either carbon tetrachloride (CCl4) or thioacetamide (TAA) were evaluated for mRNA expression of Snail1. The transcription factor expression was investigated by immunostaining and real-time quantitative RT-PCR (qRT-PCR) on in vitro and in vivo activated murine HSC. Snail1 knockdown studies on cultured HSC and on CCl4-treated mice were performed by adenoviral delivery of short-hairpin RNA; activation-related genes were quantitated by real-time qRT-PCR and Western blotting. Snail1 mRNA expression resulted upregulated in murine experimental models of liver injury and in human hepatic fibrosis. In vitro studies showed that Snail1 is expressed by HSC and that its transcription is augmented in in vitro and in vivo activated HSC compared with quiescent HSC. At the protein level, we could observe the nuclear translocation of Snail1 in activated HSC. Snail1 knockdown resulted in the downregulation of activation-related genes both in vitro and in vivo. Our data support a role for Snail1 transcription factor in the hepatic wound-healing response and its involvement in the HSC transdifferentiation process.

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965 ACID SPHINGOMYELINASE CONTROLS HEPATIC STELLATE CELL ACTIVATION AND IN VIVO LIVER FIBROSIS

Journal of Hepatology ◽

10.1016/s0168-8278(10)60966-x ◽

2010 ◽

Vol 52 ◽

pp. S373

Author(s):

A. Moles ◽

N. Tarrats ◽

A. Morales ◽

M. Dominguez ◽

R. Bataller ◽

...

Keyword(s):

Liver Fibrosis ◽

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Acid Sphingomyelinase ◽

Hepatic Stellate Cell Activation

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446. Inhibition of Hepatic Stellate Cell Activation and Liver Fibrosis by Expression of Cytoglobin In Vivo

Molecular Therapy ◽

10.1016/j.ymthe.2006.08.513 ◽

2006 ◽

Vol 13 ◽

pp. S171-S172

Author(s):

Ruian Xu ◽

Phillip Harrison ◽

Xinyan Li ◽

Miao Chen ◽

Hua Li ◽

...

Keyword(s):

Liver Fibrosis ◽

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Hepatic Stellate Cell Activation

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Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo

Clinical and Experimental Medicine ◽

10.1007/s10238-013-0229-6 ◽

2013 ◽

Vol 14 (2) ◽

pp. 141-150 ◽

Cited By ~ 25

Author(s):

Chunqiu Hao ◽

Yumei Xie ◽

Meijuan Peng ◽

Li Ma ◽

Yun Zhou ◽

...

Keyword(s):

Growth Factor ◽

Liver Fibrosis ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Tissue Growth

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Leucine-rich Repeats and Immunoglobulin 1 (LRIG1) Ameliorates Liver Fibrosis and Hepatic Stellate Cell Activation via Inhibiting Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P) Pathway

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v19i4.4114 ◽

2020 ◽

Author(s):

Wei Zhan ◽

Xin Liao ◽

Zhongsheng Chen ◽

Lianghe Li ◽

Tian Tian ◽

...

Keyword(s):

Liver Fibrosis ◽

Hepatic Stellate Cell ◽

Stellate Cell ◽

Sphingosine Kinase ◽

Sphingosine Kinase 1 ◽

Sphingosine 1 Phosphate ◽

Leucine Rich Repeats ◽

Tgf Β1

To detect the leucine-rich repeats and immunoglobulin 1 (LRIG1) ameliorated liver fibrosis and hepatic stellate cell (HSC) activation via inhibiting sphingosine kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P) pathway. C57BL/6 male mice (eight weeks old) were intraperitoneal injection with 10% carbon tetrachloride (CCl4) as an in vivo model. The LX-2 cells were induced as amodel for in vitro study by TGF-β (10 ng/mL). The Hematoxylin-eosin (HE) staining, Masson staining, and Sirius red staining results showed that CCl4 caused serious fibrosis and injury in liver tissue, high expression of type I collagen α1 chain (Col1α1) and α-smooth muscle actin (α-SMA) in liver tissue, while the LRIG1 expression level was significantly decreased in LX-2 cell lines. The LRIG1 ameliorated CCl4-induced liver fibrosis, indicated by the fibronectin, α-SMA, LRIG1, SphK1, Col1α1, fibrin Connexin 1 (Fn1), tissue inhibitor of metalloproteinase-1 (TIMP1), sphingosine-1-phosphate (S1P), transforming growth factor-beta 1 (TGF-β1) expression level changes. Similar results were observed in TGF-β1 treated of LX-2 cells. However, the effects were attenuated by treatment with LRIG1. Moreover, SphK1 inhibitors abrogated the effect of LRIG1 on fibrosis. These results demonstrated that LRIG1 improved liver fibrosis in vitro and in vivo via suppressing the SphK1/S1P pathway, indicating its potential use in the treatment of liver fibrosis.

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