MT1 but not MT2 melatonin receptor knockout decreases biliary damage and liver fibrosis during cholestatic liver injury

Hepatology ◽  
2021 ◽  
Author(s):  
Nan Wu ◽  
Guido Carpino ◽  
Ludovica Ceci ◽  
Leonardo Baiocchi ◽  
Heather Francis ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Melatonin Receptor ◽  
Cholestatic Liver Injury

scholarly journals MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis

2021 ◽  
Author(s):  
Yongfeng Song ◽  
Melanie Tran ◽  
Li Wang ◽  
Dong-Ju Shin ◽  
Jianguo Wu
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Feedback Loop ◽  
Ductular Reaction ◽  
Adeno Associated Virus ◽  
Matrix Deposition ◽  
Duct Ligation ◽  
Virus Serotype ◽  
Cholestatic Liver Injury

AbstractCholestasis causes ductular reaction in the liver where the reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition and contributing to the development and progression of cholestatic liver fibrosis. This study aims to elucidate the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation. We found that miR-200c was extremely abundant in cholangiocytes but was reduced by cholestasis in a bile duct ligation (BDL) mouse model; miR-200c was also decreased by bile acids in vitro. Phenotypically, loss of miR-200c exacerbated cholestatic liver injury, including periductular fibrosis, intrahepatic inflammation, and biliary hyperplasia in both the BDL model and the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model. We identified sestrin 1 (SESN1) as a target of miR-200c. Sesn1−/−-BDL mice showed mitigation of cholestatic liver injury. On a molecular level, the pro-proliferative IL-6/AKT feedback loop was activated in Mir200c−/− livers but was inhibited in Sesn1−/− livers upon cholestasis in mice. Furthermore, rescuing expression of miR-200c by the adeno-associated virus serotype 8 ameliorated BDL-induced liver injury in Mir200c−/− mice. Taken together, this study demonstrates that miR-200c restrains the proliferative and neuroendocrine-like activation of cholangiocytes by targeting SESN1 and inhibiting the IL-6/AKT feedback loop to protect against cholestatic liver fibrosis. Our findings provide mechanistic insights regarding biliary liver fibrosis, which may help to reveal novel therapeutic targets for the treatment of cholestatic liver injury and liver fibrosis.

257 LACK OF GP130/STAT IN HEPATOCYTES LEADS TO THE EMERGENCE OF OVAL CELLS AND EXTENSIVE LIVER FIBROSIS IN A MODEL OF CHRONIC CHOLESTATIC LIVER INJURY

2008 ◽  
Vol 48 ◽  
pp. S104
Author(s):  
W. Plum ◽  
E. Corsten ◽  
U. Dierssen ◽  
S. Erschfeld ◽  
D. Tschaharganeh ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Oval Cells ◽  
Cholestatic Liver Injury

457 Impact of MT2 Melatonin Receptor Deletion on Cellular Senescence in Cholangiocytes Isolated From Mice After Cholestatic Liver Injury

2015 ◽  
Vol 148 (4) ◽  
pp. S-980
Author(s):  
Nan Wu ◽  
Ying Wan ◽  
Yuyan Han ◽  
Tami Annable ◽  
Debolina Ray ◽  
...  
Keyword(s):  
Liver Injury ◽  
Cellular Senescence ◽  
Melatonin Receptor ◽  
Cholestatic Liver Injury

Tu1694 Regulation of Cellular Senescence Associated Liver Fibrosis By Melatonin in Cholestatic Liver Injury

2016 ◽  
Vol 150 (4) ◽  
pp. S1165
Author(s):  
Nan Wu ◽  
Fanyin Meng ◽  
Julie Venter ◽  
Konstantina Kyritsi ◽  
Heather L. Francis ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Cellular Senescence ◽  
Cholestatic Liver Injury

scholarly journals Methane-Rich Saline Counteracts Cholestasis-Induced Liver Damage via Regulating the TLR4/NF-κB/NLRP3 Inflammasome Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zeyu Li ◽  
Dongdong Chen ◽  
Yifan Jia ◽  
Yang Feng ◽  
Cong Wang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Inflammatory Cells ◽  
Protective Mechanism ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Associated Proteins ◽  
Anti Inflammatory ◽  
Cholestatic Liver Injury

Cholestatic liver injury, due to obstruction of the biliary tract or genetic defects, is often accompanied by progressive inflammation and liver fibrosis. Methane-rich saline (MRS) has anti-inflammatory properties. However, whether MRS can provide protective effect in cholestatic liver injury is still unclear. In this study, Sprague-Dawley rats received bile duct ligation (BDL) to generate a cholestatic model followed by MRS treatment (10 mL/kg, ip treatment) every 12 h after the operation to explore the potential protective mechanism of MRS in cholestatic liver injury. We found that MRS effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. MRS treatment decreased the expression of hepatic fibrosis-associated proteins to alleviate liver fibrosis. Furthermore, MRS treatment suppressed the TLR4/NF-κB pathway and further reduced the levels of proinflammatory factors. Downregulation of NF-κB subsequently reduced the NLRP3 expression to inhibit pyroptosis. Our data indicated that methane treatment prevented cholestatic liver injury via anti-inflammatory properties that involved the TLR4/NF-κB/NLRP3 signaling pathway.

Bid-mediated apoptosis does not contribute to cholestatic liver injury following bile duct ligation

2009 ◽  
Vol 47 (01) ◽  
Author(s):  
P Nalapareddy ◽  
S Schüngel ◽  
MP Manns ◽  
H Jaeschke ◽  
A Vogel
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Cholestatic Liver Injury
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