scholarly journals Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease

2012 ◽  
Vol 18 (4) ◽  
pp. 572-579 ◽  
Author(s):  
Luke Boulter ◽  
Olivier Govaere ◽  
Tom G Bird ◽  
Sorina Radulescu ◽  
Prakash Ramachandran ◽  
...  
Keyword(s):  
Liver Disease ◽  
Notch Signaling ◽  
Chronic Liver Disease ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Chronic Liver ◽  
Hepatic Progenitor Cell

scholarly journals Notch Inhibition Promotes Differentiation of Liver Progenitor Cells into Hepatocytes via sox9b Repression in Zebrafish

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jacquelyn O. Russell ◽  
Sungjin Ko ◽  
Satdarshan P. Monga ◽  
Donghun Shin
Keyword(s):  
Liver Disease ◽  
Liver Regeneration ◽  
Notch Signaling ◽  
Chronic Liver Disease ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Chronic Liver ◽  
Hepatocyte Proliferation ◽  
Hepatocyte Differentiation

Liver regeneration after most forms of injury is mediated through the proliferation of hepatocytes. However, when hepatocyte proliferation is impaired, such as during chronic liver disease, liver progenitor cells (LPCs) arising from the biliary epithelial cell (BEC) compartment can give rise to hepatocytes to mediate hepatic repair. Promotion of LPC-to-hepatocyte differentiation in patients with chronic liver disease could serve as a potentially new therapeutic option, but first requires the identification of the molecular mechanisms driving this process. Notch signaling has been identified as an important signaling pathway promoting the BEC fate during development and has also been implicated in regulating LPC differentiation during regeneration. SRY-related HMG box transcription factor 9 (Sox9) is a direct target of Notch signaling in the liver, and Sox9 has also been shown to promote the BEC fate during development. We have recently shown in a zebrafish model of LPC-driven liver regeneration that inhibition of Hdac1 activity through MS-275 treatment enhances sox9b expression in LPCs and impairs LPC-to-hepatocyte differentiation. Therefore, we hypothesized that inhibition of Notch signaling would promote LPC-to-hepatocyte differentiation by repressing sox9b expression in zebrafish. We ablated the hepatocytes of Tg(fabp10a:CFP-NTR) larvae and blocked Notch activation during liver regeneration through treatment with γ-secretase inhibitor LY411575 and demonstrated enhanced induction of Hnf4a in LPCs. Alternatively, enhancing Notch signaling via Notch3 intracellular domain (N3ICD) overexpression impaired Hnf4a induction. Hepatocyte ablation in sox9b heterozygous mutant embryos enhanced Hnf4a induction, while BEC-specific Sox9b overexpression impaired LPC-to-hepatocyte differentiation. Our results establish the Notch-Sox9b signaling axis as inhibitory to LPC-to-hepatocyte differentiation in a well-established in vivo LPC-driven liver regeneration model.

scholarly journals Morphogens and hepatic stellate cell fate regulation in chronic liver disease

2012 ◽  
Vol 27 ◽  
pp. 94-98 ◽  
Author(s):  
Hidekazu Tsukamoto ◽  
Nian-Ling Zhu ◽  
Jiaohong Wang ◽  
Kinji Asahina ◽  
Keigo Machida
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Cell Fate ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Chronic Liver

Genetic predictors of spontaneous viral elimination or chronic liver disease in hepatitis C infection

2001 ◽  
Vol 120 (5) ◽  
pp. A7-A7
Author(s):  
S ROSS ◽  
S MASCHERETTI ◽  
H HINRICHSEN ◽  
P BUGGISCH ◽  
U FOELSCH ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Hepatitis C Infection ◽  
Genetic Predictors
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