scholarly journals Chemically modified liposomes carrying TRAIL target activated hepatic stellate cells and ameliorate hepatic fibrosis in vitro and in vivo

2018 ◽  
Vol 23 (3) ◽  
pp. 1951-1962 ◽  
Author(s):  
Qinghua Li ◽  
Youcheng Ding ◽  
Xinlai Guo ◽  
Shenggen Luo ◽  
Huiren Zhuang ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chemically Modified ◽  
Activated Hepatic Stellate Cells

scholarly journals COX-2 Regulates the Proliferation and Apoptosis of Activated Hepatic Stellate Cells through CDC27

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yang Hu ◽  
Nian Fu ◽  
Li Xian Chen ◽  
Jian Hua Xiao ◽  
Xue Feng Yang
Keyword(s):  
Cell Proliferation ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis ◽  
Cox 2 ◽  
Activated Hepatic Stellate Cells

Cyclooxygenase-2 (COX-2) is an important rate-limiting enzyme in the synthesis of prostaglandins (PGs), which can be upregulated by various stimuli. COX-2 has been shown to be involved in the occurrence and development of hepatic fibrosis by regulating the proliferation and apoptosis of hepatic stellate cells (HSCs) in previous studies. The aims of the study are to study the mechanism of how COX-2 regulates the proliferation and apoptosis of HSCs and to provide new targets for the prevention and treatment of hepatic fibrosis. A short hairpin RNA targeting COX-2 was constructed, and the changes in proliferation and apoptosis of liver tissue cells and HSCs were observed, respectively. COX-2-shRNA-1 significantly suppressed the proliferation of HSCs in vivo. Moreover, knockdown of COX-2 significantly suppressed cell proliferation and accelerated cell cycle arrest and apoptosis in vitro. Among those differential genes related to cell proliferation and apoptosis, CDC27 and Sh3kbp1 were upregulated, but Plcd4 was suppressed. Mechanistically, the influence of COX-2 on HSCs partly depends on upregulating CDC27. Our results demonstrated that COX-2 regulates the proliferation and apoptosis of activated hepatic stellate cells through the CDC27 pathway. This study contributes to our understanding of the effect of COX-2 for the treatment of hepatic 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 PF2401-SF, Standardized Fraction of Salvia miltiorrhiza, Induces Apoptosis of Activated Hepatic Stellate Cells in Vitro and in Vivo

Molecules ◽  
2013 ◽  
Vol 18 (2) ◽  
pp. 2122-2134 ◽  
Author(s):  
Daya Parajuli ◽  
Eun-Jeon Park ◽  
Xian-Hua Che ◽  
Wen-Yi Jiang ◽  
Youn-Chul Kim ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Salvia Miltiorrhiza ◽  
Stellate Cells ◽  
Activated Hepatic Stellate Cells

scholarly journals Exemestane Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells and Promoting the Secretion of Interleukin 10

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ya-Hui Wang ◽  
Rong-Kun Li ◽  
Ying Fu ◽  
Jun Li ◽  
Xiao-Mei Yang ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Antioxidant Activities ◽  
Culture Media ◽  
Stellate Cells ◽  
Aromatase Activity ◽  
Duct Ligation ◽  
Anti Inflammatory

Exemestane (EXE) is an irreversible steroidal aromatase inhibitor mainly used as an adjuvant endocrine therapy for postmenopausal women suffering from breast cancer. Besides inhibiting aromatase activity, EXE has multiple biological functions, such as antiproliferation, anti-inflammatory, and antioxidant activities which are all involved in hepatic fibrosis. Therefore, we investigated the role of EXE during the progress of hepatic fibrosis. The effect of EXE on liver injury and fibrosis were assessed in two hepatic fibrosis rat models, which were induced by either carbon tetrachloride (CCl4) or bile duct ligation (BDL). The influence of EXE treatment on activation and proliferation of primary rat hepatic stellate cells (HSCs) was observedin vitro. The results showed that EXE attenuated the liver fibrosis by decreasing the collagen deposition andα-SMA expressionin vivoand inhibited the activation and proliferation of primary rat HSCsin vitro. Additionally, EXE promoted the secretion of antifibrotic and anti-inflammatory cytokine IL-10in vivoand in HSC-T6 culture media. In conclusion, our findings reveal a new function of EXE on hepatic fibrosis and prompted its latent application in liver fibrotic-related disease.

scholarly journals Silencing p53 inhibits interleukin 10-induced activated hepatic stellate cell senescence and fibrotic degradation in vivo

2020 ◽  
pp. 153537022096039
Author(s):  
Qilan Guo ◽  
Minghua Chen ◽  
Qingduo Chen ◽  
Guitao Xiao ◽  
Zhixin Chen ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Interleukin 10 ◽  
P53 Signaling ◽  
Gene Treatment ◽  
Activated Hepatic Stellate Cells ◽  
Related Proteins ◽  
P53 Signaling Pathway

Activated hepatic stellate cells are reported to play a significant role in liver fibrogenesis. Beside the phenotype reversion and apoptosis of activated hepatic stellate cells, the senescence of activated hepatic stellate cells limits liver fibrosis. Our previous researches have demonstrated that interleukin-10 could promote hepatic stellate cells senescence via p53 signaling pathway in vitro. However, the relationship between expression of p53 and senescence of activated hepatic stellate cells induced by interleukin-10 in fibrotic liver is unclear. The purpose of present study was to explore whether p53 plays a crucial role in the senescence of activated hepatic stellate cells and degradation of collagen mediated by interleukin-10. Hepatic fibrosis animal model was induced by carbon tetrachloride through intraperitoneal injection and transfection of interleukin-10 gene to liver was performed by hydrodynamic-based transfer system. Depletions of p53 in vivo and in vitro were carried out by adenovirus-based short hairpin RNA against p53. Regression of fibrosis was assessed by liver biopsy and collagen staining. Cellular senescence in the liver was observed by senescence-associated beta-galactosidase (SA-β-Gal) staining. Immunohistochemistry, immunofluorescence double staining, and Western blot analysis were used to evaluate the senescent cell and senescence-related protein expression. Our data showed that interleukin-10 gene treatment could lighten hepatic fibrosis induced by carbon tetrachloride and induce the aging of activated hepatic stellate cells accompanied by up-regulating the expression of aging-related proteins. We further demonstrated that depletion of p53 could abrogate up-regulation of interleukin-10 on the expression of senescence-related protein in vivo and vitro. Moreover, p53 knockout in fibrotic mice could block not only the senescence of activated hepatic stellate cells, but also the degradation of fibrosis induced by interleukin-10 gene intervention. Taken together, our results suggested that interleukin-10 gene treatment could attenuate carbon tetrachloride-induced hepatic fibrosis by inducing senescence of activated hepatic stellate cells in vivo, and this induction was closely related to p53 signaling pathway. Impact statement This work further expanded the knowledge of the molecular mechanisms underlying IL-10 anti-fibrogenic effect by exploring the function of p53 in IL-10-induced activated HSCs senescence and fibrotic degradation in vivo. Our data showed that IL-10 gene intervention could lighten hepatic fibrosis induced by CCL4 and induce the senescence of activated HSCs accompanied by up-regulating the expression of senescence-related proteins. In addition, depletion of p53 could abrogate up-regulation of IL-10 on the expression of aging-related proteins in vivo and vitro. Moreover, p53 knockout in fibrotic mice could block the senescence of activated HSCs and the degradation of fibrosis induced by IL-10 gene treatment. In summary, our results suggested that IL-10 gene intervention could attenuate CCL4-induced hepatic fibrosis by inducing senescence of activated HSCs in vivo, and this induction was closely related to p53 signaling pathway. Our study sheds important light into the anti-fibrogenic therapy of IL-10.

Amygdalin inhibits TGFβ1-induced activation of hepatic stellate cells (HSCs) in vitro and CCl4-induced hepatic fibrosis in rats in vivo

2021 ◽  
Vol 90 ◽  
pp. 107151
Author(s):  
Ruoyu Wang ◽  
Dong Zhang ◽  
Dan Tang ◽  
Kewei Sun ◽  
Jianping Peng ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells

IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells

2002 ◽  
Vol 282 (6) ◽  
pp. G981-G990 ◽  
Author(s):  
Philippe Mathurin ◽  
Shigang Xiong ◽  
Kusum K. Kharbanda ◽  
Nary Veal ◽  
Takeo Miyahara ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Hepatic Stellate Cells ◽  
Constitutive Expression ◽  
Stellate Cells ◽  
Mrna Levels ◽  
Pcr Cloning ◽  
Collagen Production ◽  
Activated Hepatic Stellate Cells

Interleukin (IL)-10 expression is induced in activated hepatic stellate cells (HSC) in vitro and in vivo. We analyzed expression of IL-10 receptor (IL-10R) and coreceptor cytokine receptor family (CRF2–4) in HSC. We aimed to clone and sequence partial cDNA for rat IL-10R and CRF2–4, determine their expression in activated rat HSC in vivo and in vitro, and examine the biological responsiveness of HSC to exogenous IL-10. PCR cloning and sequencing of partial rat IL-10R and CRF2–4 cDNAs revealed 86% homology with corresponding mouse sequences. In hepatic macrophages, Northern blot with cloned IL-10R cDNA detected an expected 3.5-kb transcript, and IL-10R and CRF2–4 mRNAs showed steady constitutive expression after in vitro lipopolysaccharide treatment or cholestatic liver injury. IL-10R mRNA expression, as confirmed by immunohistochemistry, was induced 20.1- and 8.6-fold in HSC from cholestatic livers and 7-day culture-activated HSC, respectively but CRF2–4 mRNA levels were unchanged. Under serum-free conditions, IL-10 had minimal effects on collagen production but reduced DNA synthesis, matrix metalloprotease-2 mRNA levels, and activity in HSC. With serum, IL-10 inhibited both collagen production and DNA synthesis but had no effect on procollagen-α1(I) mRNA levels. This shows concomitant induction of IL-10R but not CRF2–4 to that of IL-10 by activated HSC in vitro and in vivo and associated acquisition of the responsiveness to IL-10, entailing complex effects on HSC.

scholarly journals Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro

Gut ◽  
1999 ◽  
Vol 44 (1) ◽  
pp. 127-136 ◽  
Author(s):  
I Shimizu ◽  
Y Mizobuchi ◽  
M Yasuda ◽  
M Shiba ◽  
Y-R Ma ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Inhibitory Effect ◽  
Type I ◽  
Mrna Levels ◽  
Pig Serum

BackgroundHepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis.AimsTo examine the inhibitory effect of oestradiol on stellate cell activation.MethodsIn vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like cells.ResultsIn the dimethylnitrosamine and pig serum models, treatment with oestradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, reduced collagen content, lower areas of stellate cells which express α smooth muscle actin (α-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhibited type I collagen production, α-SMA expression, and cell proliferation. These findings suggest that oestradiol is a potent inhibitor of stellate cell transformation.ConclusionThe antifibrogenic role of oestradiol in the liver may contribute to the sex associated differences in the progression from hepatic fibrosis to cirrhosis.

Erratum: Study on the in vitro and in vivo activation of rat hepatic stellate cells by Raman spectroscopy

2007 ◽  
Vol 12 (5) ◽  
pp. 059801
Author(s):  
Aiguo Shen ◽  
Zhangxiu Liao ◽  
Hui Wang ◽  
Iiho Goan ◽  
Yong Wu ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Hepatic Stellate Cells ◽  
Stellate Cells
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