Geniposide suppresses liver injury in a mouse model of DDC ‐induced sclerosing cholangitis

2021 ◽  
Author(s):  
Min Wen ◽  
Yubei Liu ◽  
Ruiying Chen ◽  
Ping He ◽  
Feihua Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Sclerosing Cholangitis

Signal Transducer and Activator of Transcription 3 Protects From Liver Injury and Fibrosis in a Mouse Model of Sclerosing Cholangitis

2010 ◽  
Vol 138 (7) ◽  
pp. 2499-2508 ◽  
Author(s):  
Markus Mair ◽  
Gernot Zollner ◽  
Doris Schneller ◽  
Monica Musteanu ◽  
Peter Fickert ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Sclerosing Cholangitis ◽  
Signal Transducer ◽  
Transcription 3

NorUDCA improves liver injury and glucose sensitivity in a mouse model of obesity and steatosis

2015 ◽  
Vol 53 (05) ◽  
Author(s):  
D Steinacher ◽  
T Claudel ◽  
T Stojakovic ◽  
M Trauner
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Glucose Sensitivity

A new mouse model of sclerosing cholangitis combining toxic and immune mediated bile duct injury

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
F Glaser ◽  
B Engel ◽  
C John ◽  
T Krech ◽  
A Carambia ◽  
...  
Keyword(s):  
Bile Duct ◽  
Mouse Model ◽  
Bile Duct Injury ◽  
Sclerosing Cholangitis ◽  
Immune Mediated

Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis

Gut ◽  
2019 ◽  
Vol 68 (8) ◽  
pp. 1477-1492 ◽  
Author(s):  
Lijun Liao ◽  
Kai Markus Schneider ◽  
Eric J C Galvez ◽  
Mick Frissen ◽  
Hanns-Ulrich Marschall ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Injury ◽  
Sclerosing Cholangitis ◽  
Functional Role ◽  
Innate Immune ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Intestinal Dysbiosis ◽  
Nlrp3 Inflammasome Activation

ObjectiveThere is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut–liver crosstalk for CLD in the murine Mdr2 knockout (Mdr2−/−) model resembling human primary sclerosing cholangitis (PSC).DesignMale Mdr2−/−, Mdr2−/− crossed with hepatocyte-specific deletion of caspase-8 (Mdr2−/−/Casp8∆hepa) and wild-type (WT) control mice were housed for 8 or 52 weeks, respectively, to characterise the impact of Mdr2 deletion on liver and gut including bile acid and microbiota profiling. To block caspase activation, a pan-caspase inhibitor (IDN-7314) was administered. Finally, the functional role of Mdr2−/−-associated intestinal dysbiosis was studied by microbiota transfer experiments.ResultsMdr2−/− mice displayed an unfavourable intestinal microbiota signature and pronounced NLRP3 inflammasome activation within the gut–liver axis. Intestinal dysbiosis in Mdr2−/− mice prompted intestinal barrier dysfunction and increased bacterial translocation amplifying the hepatic NLRP3-mediated innate immune response. Transfer of Mdr2−/− microbiota into healthy WT control mice induced significant liver injury in recipient mice, highlighting the causal role of intestinal dysbiosis for disease progression. Strikingly, IDN-7314 dampened inflammasome activation, ameliorated liver injury, reversed serum bile acid profile and cholestasis-associated microbiota signature.ConclusionsMDR2-associated cholestasis triggers intestinal dysbiosis. In turn, translocation of endotoxin into the portal vein and subsequent NLRP3 inflammasome activation contribute to higher liver injury. This process does not essentially depend on caspase-8 in hepatocytes, but can be blocked by IDN-7314.

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