Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis-a serological evaluation

2012 ◽  
Vol 33 (3) ◽  
pp. 439-447 ◽  
Author(s):  
Diana J. Leeming ◽  
Inger Byrjalsen ◽  
Wladimiro Jiménez ◽  
Claus Christiansen ◽  
Morten A. Karsdal
Keyword(s):  
Extracellular Matrix ◽  
Liver Fibrosis ◽  
Rat Model ◽  
Protein Fingerprinting ◽  
Extracellular Matrix Remodelling

scholarly journals Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction

2000 ◽  
Vol 1 (4) ◽  
pp. 369-378 ◽  
Author(s):  
Marwan E El-Sabban ◽  
Khaled A Hassan ◽  
Adel E Birbari ◽  
Khalil M Bitar ◽  
Anwar B Bikhazi
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Rat Model ◽  
Extracellular Matrix Remodelling

F.N.10 PHARMACOLOGICAL ANTAGONISM OF ENDOCANNABINOID CB1 RECEPTOR AMELIORATES LIVER FIBROSIS IN A RAT MODEL OF ADVANCED CIRRHOSIS

2010 ◽  
Vol 42 ◽  
pp. S36-S37
Author(s):  
F.A. Giannone ◽  
M. Domenicali ◽  
M. Baldassarre ◽  
G. Di Pompo ◽  
M. Bernardi ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Rat Model ◽  
Cb1 Receptor ◽  
Advanced Cirrhosis

EXTRACELLULAR MATRIX REMODELLING IN A MURINE MAMMARY ADENOCARCINOMA TRANSFECTED WITH THE INTERFERON-ALPHA1 GENE

1997 ◽  
Vol 181 (1) ◽  
pp. 116-123 ◽  
Author(s):  
SUSANNA SCARPA ◽  
ANNA GIUFFRIDA ◽  
CAMILLA PALUMBO ◽  
FORTUNATA VASATURO ◽  
PAOLA SIGNORELLI ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mammary Adenocarcinoma ◽  
Extracellular Matrix Remodelling

Targeting ER protein TXNDC5 in hepatic stellate cell mitigates liver fibrosis by repressing non-canonical TGFβ signalling

Gut ◽  
2021 ◽  
pp. gutjnl-2021-325065
Author(s):  
Chen-Ting Hung ◽  
Tung-Hung Su ◽  
Yen-Ting Chen ◽  
Yueh-Feng Wu ◽  
You-Tzung Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Transforming Growth Factor Β1 ◽  
Duct Ligation ◽  
Extracellular Matrix Production ◽  
Matrix Production

Background and objectivesLiver fibrosis (LF) occurs following chronic liver injuries. Currently, there is no effective therapy for LF. Recently, we identified thioredoxin domain containing 5 (TXNDC5), an ER protein disulfide isomerase (PDI), as a critical mediator of cardiac and lung fibrosis. We aimed to determine if TXNDC5 also contributes to LF and its potential as a therapeutic target for LF.DesignHistological and transcriptome analyses on human cirrhotic livers were performed. Col1a1-GFPTg, Alb-Cre;Rosa26-tdTomato and Tie2-Cre/ERT2;Rosa26-tdTomato mice were used to determine the cell type(s) where TXNDC5 was induced following liver injury. In vitro investigations were conducted in human hepatic stellate cells (HSCs). Col1a2-Cre/ERT2;Txndc5fl/fl (Txndc5cKO) and Alb-Cre;Txndc5fl/fl (Txndc5Hep-cKO) mice were generated to delete TXNDC5 in HSCs and hepatocytes, respectively. Carbon tetrachloride treatment and bile duct ligation surgery were employed to induce liver injury/fibrosis in mice. The extent of LF was quantified using histological, imaging and biochemical analyses.ResultsTXNDC5 was upregulated markedly in human and mouse fibrotic livers, particularly in activated HSC at the fibrotic foci. TXNDC5 was induced by transforming growth factor β1 (TGFβ1) in HSCs and it was both required and sufficient for the activation, proliferation, survival and extracellular matrix production of HSC. Mechanistically, TGFβ1 induces TXNDC5 expression through increased ER stress and ATF6-mediated transcriptional regulation. In addition, TXNDC5 promotes LF by redox-dependent JNK and signal transducer and activator of transcription 3 activation in HSCs through its PDI activity, activating HSCs and making them resistant to apoptosis. HSC-specific deletion of Txndc5 reverted established LF in mice.ConclusionsER protein TXNDC5 promotes LF through redox-dependent HSC activation, proliferation and excessive extracellular matrix production. Targeting TXNDC5, therefore, could be a potential novel therapeutic strategy to ameliorate LF.

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