Cross talk between toll-like receptor-4 signaling and angiotensin-II in liver fibrosis development in the rat model of non-alcoholic steatohepatitis

2013 ◽  
Vol 28 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Yusaku Shirai ◽  
Hitoshi Yoshiji ◽  
Ryuichi Noguchi ◽  
Kosuke Kaji ◽  
Yosuke Aihara ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Liver Fibrosis ◽  
Cross Talk ◽  
Rat Model ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Alcoholic Steatohepatitis

scholarly journals Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis

2021 ◽  
Vol 13 (599) ◽  
pp. eabe1692
Author(s):  
Junjie Yu ◽  
Changyu Zhu ◽  
Xiaobo Wang ◽  
KyeongJin Kim ◽  
Alberto Bartolome ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
High Fat Diet ◽  
Therapeutic Potential ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nonalcoholic Fatty Liver ◽  
Biopsy Specimens ◽  
Nafld Activity Score ◽  
Notch Activation

Aberrant hepatocyte Notch activity is critical to the development of nonalcoholic steatohepatitis (NASH)–induced liver fibrosis, but mechanisms underlying Notch reactivation in developed liver are unclear. Here, we identified that increased expression of the Notch ligand Jagged1 (JAG1) tracked with Notch activation and nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in human liver biopsy specimens and mouse NASH models. The increase in Jag1 was mediated by hepatocyte Toll-like receptor 4 (TLR4)–nuclear factor κB (NF-κB) signaling in pericentral hepatocytes. Hepatocyte-specific Jag1 overexpression exacerbated fibrosis in mice fed a high-fat diet or a NASH-provoking diet rich in palmitate, cholesterol, and sucrose and reversed the protection afforded by hepatocyte-specific TLR4 deletion, whereas hepatocyte-specific Jag1 knockout mice were protected from NASH-induced liver fibrosis. To test therapeutic potential of this biology, we designed a Jag1-directed antisense oligonucleotide (ASO) and a hepatocyte-specific N-acetylgalactosamine (GalNAc)–modified siRNA, both of which reduced NASH diet–induced liver fibrosis in mice. Overall, these data demonstrate that increased hepatocyte Jagged1 is the proximal hit for Notch-induced liver fibrosis in mice and suggest translational potential of Jagged1 inhibitors in patients with NASH.

Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice

Gut ◽  
2012 ◽  
Vol 61 (7) ◽  
pp. 1058-1067 ◽  
Author(s):  
Dewei Ye ◽  
Francois Y L Li ◽  
Karen S L Lam ◽  
Huating Li ◽  
Weiping Jia ◽  
...  
Keyword(s):  
Binding Protein ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Alcoholic Steatohepatitis

scholarly journals Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection

2009 ◽  
Vol 51 (4) ◽  
pp. 750-757 ◽  
Author(s):  
Yonghong Li ◽  
Monica Chang ◽  
Olivia Abar ◽  
Veronica Garcia ◽  
Charles Rowland ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Chronic Hepatitis C ◽  
Toll Like Receptor ◽  
Hepatitis C Infection ◽  
Toll Like Receptor 4 ◽  
Multiple Variants
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