Notch signaling regulates formation of the three‐dimensional architecture of intrahepatic bile ducts in mice

Erin E. Sparks, Kari A. Huppert, Melanie A. Brown, M. Kay Washington, Stacey S. Huppert – 26 March 2010 – Alagille syndrome, a chronic hepatobiliary disease, is characterized by paucity of intrahepatic bile ducts (IHBDs). To determine the impact of Notch signaling specifically on IHBD arborization, we studied the influence of both chronic gain and loss of Notch function on the intact three‐dimensional IHBD structure using a series of mutant mouse models and a resin casting method.

Interplay of hepatic and myeloid signal transducer and activator of transcription 3 in facilitating liver regeneration via tempering innate immunity

Hua Wang, Ogyi Park, Fouad Lafdil, Kezhen Shen, Norio Horiguchi, Shi Yin, Xin‐Yuan Fu, George Kunos, Bin Gao – 26 March 2010 – Liver regeneration triggered by two‐thirds partial hepatectomy is accompanied by elevated hepatic levels of endotoxin, which contributes to the regenerative process, but liver inflammation and apoptosis remain paradoxically limited.

Genome‐wide tissue‐specific farnesoid X receptor binding in mouse liver and intestine

Ann M. Thomas, Steven N. Hart, Bo Kong, Jianwen Fang, Xiao‐bo Zhong, Grace L. Guo – 26 March 2010 – Farnesoid X receptor (FXR) is a bile acid‐activated transcription factor belonging to the nuclear receptor superfamily. FXR is highly expressed in liver and intestine and crosstalk mediated by FXR in these two organs is critical in maintaining bile acid homeostasis. FXR deficiency has been implicated in many liver and intestine diseases. However, regulation of transcription by FXR at the genomic level is not known.

Serotonin promotes tumor growth in human hepatocellular cancer

Christopher Soll, Jae Hwi Jang, Marc‐Oliver Riener, Wolfgang Moritz, Peter Johannes Wild, Rolf Graf, Pierre‐Alain Clavien – 26 March 2010 – In addition to its function as a neurotransmitter and vascular active molecule, serotonin is also a mitogen for hepatocytes and promotes liver regeneration. A possible role in hepatocellular cancer has not yet been investigated. Human hepatocellular cancer cell lines Huh7 and HepG2 were used to assess the function of serotonin in these cell lines.

Bioluminescence imaging allows measuring CD8 T cell function in the liver

Dirk Stabenow, Marianne Frings, Christina Trück, Katja Gärtner, Irmgard Förster, Christian Kurts, Thomas Tüting, Margarete Odenthal, Hans‐Peter Dienes, Karin Cederbrant, Ulrike Protzer, Percy A. Knolle – 26 March 2010 – In vivo evaluation of CD8 T cell effector (cytotoxic T lymphocyte [CTL]) function in peripheral organs such as the liver is currently not possible but would greatly improve our understanding of local immune regulation, because simple determination of antigen‐specific CTL numbers does not predict the outcome of immune responses.

Hepatocyte‐specific deletion of the antiapoptotic protein myeloid cell leukemia‐1 triggers proliferation and hepatocarcinogenesis in mice

Achim Weber, Regina Boger, Binje Vick, Toni Urbanik, Johannes Haybaeck, Stefan Zoller, Andreas Teufel, Peter H. Krammer, Joseph T. Opferman, Peter R. Galle, Marcus Schuchmann, Mathias Heikenwalder, Henning Schulze‐Bergkamen – 26 March 2010 – Regulation of hepatocellular apoptosis is crucial for liver homeostasis. Increased sensitivity of hepatocytes toward apoptosis results in chronic liver injury, whereas apoptosis resistance is linked to hepatocarcinogenesis and nonresponsiveness to therapy‐induced cell death.

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