Mo1373 - Knockout of Secretin/Secretin Receptor Axis (SCT/SR) Reduces Liver Fibrosis by Angiogenesis-Dependent Reduced Senescence of Cholangiocytes but Increased Senescence of Hepatic Stellate Cells (HSCS) in the MDR2 −/− Mouse Model of Primary Sclerosing Cholangitis (PSC)

2018 ◽  
Vol 154 (6) ◽  
pp. S-1185
Author(s):  
Tianhao Zhou ◽  
Konstantina Kyritsi ◽  
Nan Wu ◽  
Julie Venter ◽  
Heather L. Francis ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Primary Sclerosing Cholangitis ◽  
Hepatic Stellate Cells ◽  
Sclerosing Cholangitis ◽  
Stellate Cells ◽  
Secretin Receptor

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

scholarly journals Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR‐200b down‐regulation

2017 ◽  
Vol 31 (10) ◽  
pp. 4305-4324 ◽  
Author(s):  
Nan Wu ◽  
Fanyin Meng ◽  
Tianhao Zhou ◽  
Yuyan Han ◽  
Lindsey Kennedy ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Down Regulation

Sa.93. The CYP450 Mouse Model for Autoimmune Liver Disease: Virus-induced Activation of Hepatic Stellate Cells Causes Liver Fibrosis

2008 ◽  
Vol 127 ◽  
pp. S111
Author(s):  
Edith Hintermann ◽  
Martin Holdener ◽  
Monika Bayer ◽  
Michael Manns ◽  
Matthias von Herrath ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Disease Virus ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Autoimmune Liver Disease

Dynamics of Sept4 expression in fibrotic livers of mice infected with Schistosoma japonicum

Parasitology ◽  
2011 ◽  
Vol 138 (8) ◽  
pp. 1003-1010 ◽  
Author(s):  
Y. N. DUAN ◽  
H. Y. QIAN ◽  
Y. W. QIN ◽  
D. D. ZHU ◽  
X. X. HE ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Schistosoma Japonicum ◽  
Hepatic Stellate Cells ◽  
Immunohistochemical Staining ◽  
Smooth Muscle Actin ◽  
Stellate Cells ◽  
Muscle Actin ◽  
Qrt Pcr

SUMMARYIn order to investigate the dynamics of Septin4 (Sept4) expression and its function in the formation of fibrotic livers in mice infected with Schistosoma japonicum, we constructed the mouse model of S. japonicum egg-induced liver fibrosis for 24 weeks. Immunohistochemical staining, qRT-PCR and Western blot were used to detect the expression of Sept4 and α-smooth muscle actin (α-SMA). We found Sept4 localized in the perisinusoidal space where hepatic stellate cells (HSCs) distribute in the periphery of circumoval granulomas and the portal venule. The expression of Sept4 and α-SMA had a similar significant tendency of an up-regulation to a peak at 12 weeks post-infection (p.i.) followed by a down-regulation. At 24 weeks p.i. both were at a low level. These results suggest that Sept4 and α-SMA may interact together in HSCs. Based on this evidence, we hypothesize that Sept4 seems to be involved in the formation of inflammatory granulomata and subsequent liver fibrosis by regulating HSCs activation.

scholarly journals Downregulation of p16 Decreases Biliary Damage and Liver Fibrosis in the Mdr2/ Mouse Model of Primary Sclerosing Cholangitis

2020 ◽  
Vol 20 (2) ◽  
pp. 89-103
Author(s):  
Konstantina Kyritsi ◽  
Heather Francis ◽  
Tianhao Zhou ◽  
Ludovica Ceci ◽  
Nan Wu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Primary Sclerosing Cholangitis ◽  
Hepatic Fibrosis ◽  
Sclerosing Cholangitis ◽  
Transforming Growth Factor ◽  
Normal Values ◽  
Intrahepatic Bile Duct ◽  
Sirtuin 1

Biliary senescence and hepatic fibrosis are hallmarks of cholangiopathies including primary sclerosing cholangitis (PSC). Senescent cholangiocytes display senescence-associated secretory phenotypes [SASPs, e.g., transforming growth factor-1 (TGF-1)] that further increase biliary senescence (by an autocrine loop) and trigger liver fibrosis by paracrine mechanisms. The aim of this study was to determine the effect of p16 inhibition and role of the TGF-1/microRNA (miR)-34a/sirtuin 1 (SIRT1) axis in biliary damage and liver fibrosis in the Mdr2/ mouse model of PSC. We treated (i) in vivo male wild-type (WT) and Mdr2/ mice with p16 Vivo-Morpholino or controls before measuring biliary mass [intrahepatic bile duct mass (IBDM)] and senescence, biliary SASP levels, and liver fibrosis, and (ii) in vitro intrahepatic murine cholangiocyte lines (IMCLs) with small interfering RNA against p16 before measuring the mRNA expression of proliferation, senescence, and fibrosis markers. p16 and miR-34a increased but SIRT1 decreased in Mdr2/ mice and PSC human liver samples compared to controls. p16 immunoreactivity and biliary senescence and SASP levels increased in Mdr2/ mice but decreased in Mdr2/ mice treated with p16 Vivo-Morpholino. The increase in IBDM and hepatic fibrosis (observed in Mdr2/ mice) returned to normal values in Mdr2/ mice treated with p16 Vivo-Morpholino. TGF-1 immunoreactivity and biliary SASPs levels were higher in Mdr2/ compared to those of WT mice but returned to normal values in Mdr2/ mice treated with p16 Vivo-Morpholino. The expression of fibrosis/senescence markers decreased in cholangiocytes from Mdr2/ mice treated with p16 Vivo-Morpholino (compared to Mdr2/ mice) and in IMCLs (after p16 silencing) compared to controls. Modulation of the TGF-1/miR-34a/SIRT1 axis may be important in the management of PSC phenotypes.

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