scholarly journals AMP-activated protein kinase activator, HL156A reduces thioacetamide-induced liver fibrosis in mice and inhibits the activation of cultured hepatic stellate cells and macrophages

2016 ◽  
Vol 49 (4) ◽  
pp. 1407-1414 ◽  
Author(s):  
Hye Shin Lee ◽  
Hyun-Sang Shin ◽  
Jinhyeok Choi ◽  
Sung-Jin Bae ◽  
Hee-Jun Wee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) regulates the activation process of hepatic stellate cells

2008 ◽  
Vol 40 (5) ◽  
pp. A33
Author(s):  
C. Bertolani ◽  
A. Caligiuri ◽  
F. Vizzutti ◽  
C. Tosti Guerra ◽  
M. Pinzani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Activation Process ◽  
Amp Activated Protein Kinase

scholarly journals Berberine Inhibition of Fibrogenesis in a Rat Model of Liver Fibrosis and in Hepatic Stellate Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ning Wang ◽  
Qihe Xu ◽  
Hor Yue Tan ◽  
Ming Hong ◽  
Sha Li ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Rat Model ◽  
Hepatic Stellate Cells ◽  
Smooth Muscle Actin ◽  
Stellate Cells ◽  
Molecular Approaches ◽  
Duct Ligation ◽  
High Doses ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase

Aim.To examine the effect of berberine (BBR) on liver fibrosis and its possible mechanisms through direct effects on hepatic stellate cells (HSC).Methods.The antifibrotic effect of BBR was determined in a rat model of bile duct ligation- (BDL-) induced liver fibrosis. Multiple cellular and molecular approaches were introduced to examine the effects of BBR on HSC.Results.BBR potently inhibited hepatic fibrosis induced by BDL in rats. It exhibited cytotoxicity to activated HSC at doses nontoxic to hepatocytes. High doses of BBR induced apoptosis of activated HSC, which was mediated by loss of mitochondrial membrane potential and Bcl-2/Bax imbalance. Low doses of BBR suppressed activation of HSC as evidenced by the inhibition ofα-smooth muscle actin (α-SMA) expression and cell motility. BBR did not affect Smad2/3 phosphorylation but significantly activated 5′ AMP-activated protein kinase (AMPK) signalling, which was responsible for the transcriptional inhibition by BBR of profibrogenic factorsα-SMA and collagen in HSC.Conclusion.BBR is a promising agent for treating liver fibrosis through multiple mechanisms, at least partially by directly targeting HSC and by inhibiting the AMPK pathway. Its value as an antifibrotic drug in patients with liver disease deserves further investigation.

HMGB1-induced autophagy facilitates hepatic stellate cells activation: a new pathway in liver fibrosis

2018 ◽  
Vol 132 (15) ◽  
pp. 1645-1667 ◽  
Author(s):  
Jing Li ◽  
Chuxiong Zeng ◽  
Beishi Zheng ◽  
Chun Liu ◽  
Min Tang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Mammalian Target Of Rapamycin ◽  
High Mobility ◽  
Stellate Cells ◽  
Mitogen Activated Protein Kinase ◽  
Antifibrotic Therapy ◽  
Transmission Electron ◽  
Mitogen Activated Protein

High-mobility group box-1 (HMGB1) plays a context-dependent role in autophagy, which is required for hepatic stellate cells (HSCs) activation. However, the significance of HMGB1-induced HSCs autophagy in liver fibrosis has not been elucidated. Here, we first documented an enrichment of peripheral and intrahepatic HMGB1 signal in hepatitis B virus (HBV)-related liver fibrosis progression, and presented a direct evidence of anatomic proximity of HMGB1 with a-SMA (a marker for HSCs activation) in cirrhotic liver specimens. Then, we demonstrated the autophagy-inducing effects by serum-sourced HMGB1 in both primary murine HSCs and human HSCs cell line (LX-2), reflected by increased number of autophagic vacuoles (AVs) under the transmission electron microscope (TEM) and up-regulated protein expression of lipidated microtubule-associated light chain 3 (LC3-II) (a marker for autophagosome) in Western blot analysis. Intriguingly, there is a possible translocation of endogenous HMGB1 from the nucleus to cytoplasm to extracellular space, during exogenous HMGB1-induced HSCs autophagy. Meanwhile, the dose- and time-dependent effects by recombinant HMGB1 (rHMGB1) in enhancing LX-2 autophagy and fibrogenesis have been revealed with activated extracellular regulated protein kinase (ERK)/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) and restrained mammalian target of rapamycin (mTOR)/STAT3 signaling pathways. Additionally, the ERK or JNK inhibitor could not only inhibit rHMGB1-induced autophagy and fibrogenesis in LX-2 cells, but also restore the suppressed mTOR and STAT3 pathways. Furthermore, using LC3-siRNA transfected LX-2, we found HMGB1-induced fibrogenesis is dependent on its autophagy-inducing effects. Finally, we elucidated the involvement of extracellular HMGB1-receptor for advenced glycation end product (RAGE) axis and endogenous HMGB1 in exogenous HMGB1-induced effects. Our findings could open new perspectives in developing an antifibrotic therapy by targetting the HSCs autophagy.

467 IMPACT OF AMP-ACTIVATED PROTEIN KINASE (AMPK) ON THE CONTROL OF HEPATIC STELLATE CELLS (HSCS) ACTIVATION IN VITRO

2008 ◽  
Vol 48 ◽  
pp. S178
Author(s):  
A. da Silva Morais ◽  
J. Abarca-Quinones ◽  
L. Hue ◽  
B. Viollet ◽  
Y. Horsmans ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Amp Activated Protein Kinase

462 AMP-ACTIVATED PROTEIN KINASE (AMPK) REGULATES THE ACTIVATION PROCESS OF HEPATIC STELLATE CELLS

2008 ◽  
Vol 48 ◽  
pp. S176
Author(s):  
C. Bertolani ◽  
A. Caligiuri ◽  
F. Vizzutti ◽  
C. Tosti Guerra ◽  
M. Pinzani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Activation Process ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) blocks the effects of PDGF by PI3K-independent signals and is downregulated during in vivo activation of hepatic stellate cells

2007 ◽  
Vol 39 (3) ◽  
pp. A16
Author(s):  
Cristiana Bertolani ◽  
Alessandra Caligiuri ◽  
Cristina Tosti Guerra ◽  
Sara Aleffi ◽  
Sara Galastri ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Amp Activated Protein Kinase

289 THE ACTIN CYTOSKELETON AS A NOVEL TARGET OF AMP-ACTIVATED PROTEIN KINASE (AMPK) IN HEPATIC STELLATE CELLS

2009 ◽  
Vol 50 ◽  
pp. S113
Author(s):  
K. Rombouts ◽  
C. Tosti Guerra ◽  
A. Caligiuri ◽  
C. Bertolani ◽  
E. Rovida ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Actin Cytoskeleton ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Novel Target ◽  
Amp Activated Protein Kinase
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