Peroxisome proliferator-activated receptors gamma reverses hepatic nutritional fibrosis in mice and suppresses activation of hepatic stellate cells in vitro

2010 ◽  
Vol 42 (6) ◽  
pp. 948-957 ◽  
Author(s):  
Jun Yu ◽  
Sui Zhang ◽  
Eagle S.H. Chu ◽  
Minnie Y.Y. Go ◽  
Rebecca H.Y. Lau ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Curcumin Inhibits srebp-2 Expression in Activated Hepatic Stellate Cells in Vitro by Reducing the Activity of Specificity Protein-1

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5384-5394 ◽  
Author(s):  
Qiaohua Kang ◽  
Anping Chen
Keyword(s):  
Gene Expression ◽  
Hepatic Stellate Cells ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Stellate Cells ◽  
Peroxisome Proliferator ◽  
Specificity Protein 1 ◽  
Gc Box ◽  
Specificity Protein

Abstract Elevated levels of cholesterol/low-density lipoprotein (LDL) are a risk factor for the development of nonalcoholic steatohepatitis and its associated hepatic fibrosis. However, underlying mechanisms remain elusive. We previously reported that curcumin induced gene expression of peroxisome proliferator-activated receptor (PPAR)-γ and stimulated its activity, leading to the inhibition of the activation of hepatic stellate cells (HSCs), the major effector cells during hepatic fibrogenesis. We recently showed that curcumin suppressed gene expression of LDL receptor in activated HSCs in vitro by repressing gene expression of the transcription factor sterol regulatory element binding protein-2 (SREBP-2), leading to the reduction in the level of intracellular cholesterol in HSCs and to the attenuation of the stimulatory effects of LDL on HSCs activation. The current study aimed at exploring molecular mechanisms by which curcumin inhibits srebp-2 expression in HSCs. Promoter deletion assays, mutagenesis assays, and EMSAs localize a specificity protein-1 (SP-1) binding GC-box in the srebp-2 promoter, which is responsible for enhancing the promoter activity and responding to curcumin in HSCs. Curcumin suppresses gene expression of SP-1 and reduces its trans-activation activity, which are mediated by the activation of PPARγ. The inhibitory effect of curcumin on SP-1 binding to the GC-box is confirmed by chromatin immuno-precipitation. In summary, our results demonstrate that curcumin inhibits srebp-2 expression in cultured HSCs by activating PPARγ and reducing the SP-1 activity, leading to the repression of ldlr expression. These results provide novel insights into molecular mechanisms by which curcumin inhibits LDL-induced HSC activation.

503 THE REGULATIVE EFFECTS OF FAK-RELATED NON-KINASE ON IN VITRO HEPATIC STELLATE CELLS COLLAGEN METABOLISM

2008 ◽  
Vol 48 ◽  
pp. S190
Author(s):  
J. Wei ◽  
X.L. Zhang ◽  
Z.N. Dun ◽  
S.R. Xie ◽  
J.G. Shen ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Collagen Metabolism

Gli2-regulated activation of hepatic stellate cells and liver fibrosis by TGF-β signaling

2021 ◽  
Author(s):  
Junyan Yan ◽  
Baowei Hu ◽  
Wenjie Shi ◽  
Xiaoyi Wang ◽  
Jiayuan Shen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Conditional Knockout ◽  
Rna Seq ◽  
Expression Levels ◽  
Liver Fibrogenesis ◽  
Hh Signaling ◽  
Signaling Activity

The Hedgehog (Hh) signaling pathway is correlated with hepatic stellate cells (HSCs) activation and liver fibrosis. Gli2 is a key transcription effector of Hh signaling. However, the role of Gli2 in HSC-mediated liver fibrosis progression is largely unknown. In the present study, we investigated the effect of Gli2 on liver fibrogenesis and its possible mechanism using conditional knockout (cKO) Gli2 mice and HSC models. Wild-type (WT) and GFAP-CreERT;Gli2flox/flox male mice were exposed to CCl4 for one month to induce liver fibrosis. Primary HSCs were isolated from mice and the transition of HSCs into a myofibroblastic phenotype was evaluated. Livers from mice underwent histological, immunohistochemical, and immunofluorescence analyses. The expression levels of proteins and genes were evaluated by Western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RNA-seq was used to screen differentially expressed genes. Results showed that CCl4 treatment induced liver fibrosis, promoted HSCs activation and proliferation, and up-regulated Hh signaling activity. The cKO of Gli2 in GFAP-CreERT;Gli2flox/flox mice decreased liver fibrosis as well as HSC activation and proliferation. In vitro studies showed that KO of Gli2 in HSCs blocked cell proliferation and activation by decrease of cyclin D1/D2 expression. The RNA-seq results revealed that the expression levels TGF-β1 ligands were down-regulated in Gli2 KO HSCs. Furthermore, overexpression of Gli2 rescued proliferation and activation of HSCs by up-regulation of TGF-β signaling activity. Our data demonstrated that Gli2 regulated HSC activation and liver fibrosis by TGF-β signaling, thus providing support for future Gli2-based investigations of liver fibrosis therapy.

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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