Sphingosine‐1‐phosphate promotes tumor development and liver fibrosis in mouse model of congestive hepatopathy

Hepatology ◽  
2021 ◽  
Author(s):  
Hironari Kawai ◽  
Yosuke Osawa ◽  
Michitaka Matsuda ◽  
Tomoyuki Tsunoda ◽  
Keisuke Yanagida ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Tumor Development ◽  
Sphingosine 1 Phosphate ◽  
Congestive Hepatopathy

Active role of sphingosine-1-phosphate in promoting peripheral-dominant liver fibrosis in mice model of congestive hepatopathy

2020 ◽  
Vol 73 ◽  
pp. S518
Author(s):  
Hironari Kawai ◽  
Yosuke Osawa ◽  
Yuriko Tsutsui ◽  
Yuichi Yoshida ◽  
Taizo Mori ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Active Role ◽  
Mice Model ◽  
Sphingosine 1 Phosphate ◽  
Congestive Hepatopathy

scholarly journals Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer

2010 ◽  
Vol 107 (46) ◽  
pp. 19997-20002 ◽  
Author(s):  
F. Su ◽  
K. R. Kozak ◽  
S. Imaizumi ◽  
F. Gao ◽  
M. W. Amneus ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Tumor Development ◽  
Apolipoprotein A ◽  
Mimetic Peptides

The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemia

2009 ◽  
Vol 389 (2) ◽  
pp. 251-256 ◽  
Author(s):  
Bozena Czech ◽  
Waltraud Pfeilschifter ◽  
Niloufar Mazaheri-Omrani ◽  
Marc André Strobel ◽  
Timo Kahles ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Mouse Model ◽  
Neurological Outcome ◽  
Lesion Size ◽  
Sphingosine 1 Phosphate

Mouse model and human patient data suggest critical roles for Pten and p53 in suppressing POLE mutant tumor development

2021 ◽  
Author(s):  
Vivian S Park ◽  
Meijuan JS Sun ◽  
Wesley D Frey ◽  
Leonard G Williams ◽  
Karl P Hodel ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mouse Model ◽  
Genome Stability ◽  
Nuclear Dna ◽  
Tumor Development ◽  
Base Substitution ◽  
Human Patient ◽  
Mutation Burden ◽  
P53 Activation ◽  
Subsequent Loss

Mutations in the exonuclease domain of POLE are associated with tumors harboring very high mutation burdens. The mechanisms linking this significant mutation accumulation and tumor development remain poorly understood. Pole+/P286R;Trp53+/- mice showed accelerated cancer mortality compared to Pole+/P286R;Trp53+/+ mice. Cells from Pole+/P286R mice showed increased p53 activation, and subsequent loss of p53 permitted rapid growth, implicating canonical p53 loss of heterozygosity in POLE mutant tumor growth. Somewhat surprisingly, however, p53 status had no effect on tumor mutation burden or single base substitution signatures in POLE mutant tumors from mice or humans. Pten has important roles in maintaining genome stability. We find that PTEN mutations are highly enriched in human POLE mutant tumors, including many in POLE signature contexts. One such signature mutation, PTEN-F341V, was previously shown in a mouse model to specifically decrease nuclear Pten and lead to increased DNA damage. We found tumors in Pole+/P286R mice that spontaneously acquired PtenF341V mutations and were associated with significantly reduced nuclear Pten and elevated DNA damage. Taken together with recent published work, our results support the idea that POLE-mediated hypermutagenesis is necessary, but not entirely sufficient, for tumorigenesis. Disabling surveillance of nuclear DNA damage is a likely sufficient factor.

scholarly journals Hepatoprotective Effect of MMP-19 Deficiency in a Mouse Model of Chronic Liver Fibrosis

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46271 ◽  
Author(s):  
Marketa Jirouskova ◽  
Olga Zbodakova ◽  
Martin Gregor ◽  
Karel Chalupsky ◽  
Lenka Sarnova ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Chronic Liver ◽  
Hepatoprotective Effect

scholarly journals YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Zheng ◽  
Jiaqian Luo ◽  
Yifan Yang ◽  
Rui Dong ◽  
Fa-Xing Yu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Biliary Atresia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Hippo Signaling ◽  
Mice Model ◽  
Hippo Signaling Pathway ◽  
Ductal Cells

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.

scholarly journals Deregulation of energy metabolism promotes antifibrotic effects in human hepatic stellate cells and prevents liver fibrosis in a mouse model

2016 ◽  
Vol 469 (3) ◽  
pp. 463-469 ◽  
Author(s):  
Swathi Karthikeyan ◽  
James J. Potter ◽  
Jean-Francois Geschwind ◽  
Surojit Sur ◽  
James P. Hamilton ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Hepatic Stellate Cells ◽  
Stellate Cells
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