scholarly journals Lipoprotein Lipase Up‐regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice

2019 ◽  
Vol 3 (8) ◽  
pp. 1098-1112 ◽  
Author(s):  
Toshiaki Teratani ◽  
Kengo Tomita ◽  
Hirotaka Furuhashi ◽  
Nao Sugihara ◽  
Masaaki Higashiyama ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Lipoprotein Lipase ◽  
Nonalcoholic Steatohepatitis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells

Su1499 - Lipoprotein Lipase in Hepatic Stellate Cells Exaggerates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice

2018 ◽  
Vol 154 (6) ◽  
pp. S-1159
Author(s):  
Nao Sugihara ◽  
Kengo Tomita ◽  
Hirotaka Furuhashi ◽  
Takeshi Takajo ◽  
Chie Kurihara ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Lipoprotein Lipase ◽  
Nonalcoholic Steatohepatitis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells

Free cholesterol accumulation in hepatic stellate cells: Mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice

Hepatology ◽  
2013 ◽  
Vol 59 (1) ◽  
pp. 154-169 ◽  
Author(s):  
Kengo Tomita ◽  
Toshiaki Teratani ◽  
Takahiro Suzuki ◽  
Motonori Shimizu ◽  
Hirokazu Sato ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Nonalcoholic Steatohepatitis ◽  
Hepatic Stellate Cells ◽  
Free Cholesterol ◽  
Stellate Cells ◽  
Cholesterol Accumulation

scholarly journals Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis

2018 ◽  
Vol 10 (468) ◽  
pp. eaat0344 ◽  
Author(s):  
Changyu Zhu ◽  
KyeongJin Kim ◽  
Xiaobo Wang ◽  
Alberto Bartolome ◽  
Marcela Salomao ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Nonalcoholic Steatohepatitis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Cross Sectional Study ◽  
Loss Of Function ◽  
Sectional Study ◽  
Cross Sectional ◽  
Notch Activity ◽  
Notch Activation

Fibrosis is the major determinant of morbidity and mortality in patients with nonalcoholic steatohepatitis (NASH) but has no approved pharmacotherapy in part because of incomplete understanding of its pathogenic mechanisms. Here, we report that hepatocyte Notch activity tracks with disease severity and treatment response in patients with NASH and is similarly increased in a mouse model of diet-induced NASH and liver fibrosis. Hepatocyte-specific Notch loss-of-function mouse models showed attenuated NASH-associated liver fibrosis, demonstrating causality to obesity-induced liver pathology. Conversely, forced activation of hepatocyte Notch induced fibrosis in both chow- and NASH diet–fed mice by increasing Sox9-dependent Osteopontin (Opn) expression and secretion from hepatocytes, which activate resident hepatic stellate cells. In a cross-sectional study, we found that OPN explains the positive correlation between liver Notch activity and fibrosis stage in patients. Further, we developed a Notch inhibitor [Nicastrinantisense oligonucleotide (NcstASO)] that reduced fibrosis in NASH diet–fed mice. In summary, these studies demonstrate the pathological role and therapeutic accessibility of the maladaptive hepatocyte Notch response in NASH-associated liver fibrosis.

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