Activation of LXRs prevents bile acid toxicity and cholestasis in female mice

Hirdesh Uppal, Simrat P.S. Saini, Antonio Moschetta, Ying Mu, Jie Zhou, Haibiao Gong, Yonggong Zhai, Songrong Ren, George K. Michalopoulos, David J. Mangelsdorf, Wen Xie – 26 January 2007 – Liver X receptors (LXRs) have been identified as sterol sensors that regulate cholesterol and lipid homeostasis and macrophage functions. In this study, we found that LXRs also affect sensitivity to bile acid toxicity and cholestasis.

The role of chrysin and the Ah receptor in induction of the human UGT1A1 gene in vitro and in transgenic UGT1 mice

Jessica A. Bonzo, Alain Bélanger, Robert H. Tukey – 26 January 2007 – The flavonoid chrysin is an important dietary substance and induces UGT1A1 protein expression in cell culture. As a representative of the class of dietary flavonoids, clinical investigations have been considered as a means of inducing hepatic UGT1A1 expression. We demonstrate the necessity of a xenobiotic response element (XRE) in support of chrysin induction of UGT1A1 in the human hepatoma cell line HepG2.

Activation of vascular adhesion protein‐1 on liver endothelium results in an NF‐κB–dependent increase in lymphocyte adhesion

Patricia F. Lalor, Phoebe Jun Sun, Chris J. Weston, Azucena Martin‐Santos, Michael J. O. Wakelam, David H. Adams – 26 January 2007 – Vascular adhesion protein‐1 (VAP‐1) is an adhesion molecule and amine oxidase that is expressed at high levels in the human liver. It promotes leukocyte adhesion to the liver in vivo and drives lymphocyte transmigration across hepatic sinusoidal endothelial cells in vitro.

Hepatic HNF4α deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes

Vesna S. Stanulović, Irene Kyrmizi, Marianna Kruithof‐de Julio, Maarten Hoogenkamp, Jacqueline L. M. Vermeulen, Jan M. Ruijter, Iannis Talianidis, Theodorus B. M. Hakvoort, Wouter H. Lamers – 26 January 2007 – In liver, most genes are expressed with a porto‐central gradient. The transcription factor hepatic nuclear‐factor4α (HNF4α) is associated with 12% of the genes in adult liver, but its involvement in zonation of gene expression has not been investigated.

Opposing roles of gp130‐mediated STAT‐3 and ERK‐1/2 signaling in liver progenitor cell migration and proliferation

George C. T. Yeoh, Matthias Ernst, Stefan Rose‐John, Barbara Akhurst, Christine Payne, Sarah Long, Warren Alexander, Ben Croker, Dianne Grail, Vance B. Matthews – 26 January 2007 – Gp130‐mediated IL‐6 signaling may play a role in oval cell proliferation in vivo. Levels of IL‐6 are elevated in livers of mice treated with a choline‐deficient ethionine‐supplemented (CDE) diet that induces oval cells, and there is a reduction of oval cells in IL‐6 knockout mice. The CDE diet recapitulates characteristics of chronic liver injury in humans.

Liver‐specific loss of β‐catenin results in delayed hepatocyte proliferation after partial hepatectomy

Shigeki Sekine, Pedro J. A. Gutiérrez, Billy Yu‐Ang Lan, Sandy Feng, Matthias Hebrok – 26 January 2007 – Recent studies have suggested that β‐catenin is involved in the regulation of hepatocyte proliferation in multiple contexts, including organ development and tumorigenesis. We explored the role of β‐catenin during liver regeneration using T cell factor/lymphoid enhancer factor (TCF/LEF)‐reporter mice (TOPGal mice) and liver‐specific β‐catenin knockout mice.

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