Hypoxia‐inducible factor 1α is up‐regulated by oncostatin M and participates in oncostatin M signaling

Stefan Vollmer, Valérie Kappler, Jakub Kaczor, Daniela Flügel, Catherine Rolvering, Nobuyuki Kato, Thomas Kietzmann, Iris Behrmann, Claude Haan – 23 June 2009 – The interleukin‐6–type cytokine oncostatin M (OSM) acts via the Janus kinase/signal transducer and activator of transcription pathway as well as via activation of mitogen‐activated protein kinases and is known to critically regulate processes such as liver development and regeneration, hematopoiesis, and angiogenesis, which are also determined by hypoxia with the hypoxia‐inducible factor 1α (HIF1α) as a key component.

Human immunodeficiency virus and hepatitis C infections induce distinct immunologic imprints in peripheral mononuclear cells

Shyam Kottilil, Michael Y. Yan, Kristin N. Reitano, Xiaozhen Zhang, Richard Lempicki, Gregg Roby, Marybeth Daucher, Jun Yang, Karoll J. Cortez, Marc Ghany, Michael A. Polis, Anthony S. Fauci – 23 June 2009 – Coinfection with hepatitis C virus (HCV) is present in one‐third of all human immunodeficiency virus (HIV)‐infected individuals in the United States and is associated with rapid progression of liver fibrosis and poor response to pegylated interferon (IFN) and ribavirin.

HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis‐related morbidity

Lyle C. Gurrin, Nadine A. Bertalli, Gregory W. Dalton, Nicholas J. Osborne, Clare C. Constantine, Christine E. McLaren, Dallas R. English, Dorota M. Gertig, Martin B. Delatycki, Amanda J. Nicoll, Melissa C. Southey, John L. Hopper, Graham G. Giles, Gregory J. Anderson, John K. Olynyk, Lawrie W. Powell, Katrina J. Allen, HealthIron Study Investigators – 23 June 2009 – The risk of hemochromatosis‐related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D).

S6K1 deficiency protects against apoptosis in hepatocytes

Águeda González‐Rodriguez, Javier Alba, Valeri Zimmerman, Sara C. Kozma, Ángela M. Valverde – 23 June 2009 – The mammalian target of rapamycin (mTOR)/S6K1 signaling pathway controls cell growth and proliferation. To assess the importance of S6K1 in the balance between death and survival in the liver, we have generated immortalized hepatocyte cell lines from wild‐type and S6K1‐deficient (S6K1−/−) mice. In S6K1−/− hepatocytes, caspase‐8 and the pro‐apoptotic protein Bid were constitutively down‐regulated as compared with wild‐type.

PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression

Patrick Labonté, Syntia Begley, Carl Guévin, Marie‐Claude Asselin, Nasha Nassoury, Gaétan Mayer, Annik Prat, Nabil G. Seidah – 23 June 2009 – Human PCSK9 is known to enhance the degradation of membrane‐bound receptors such as the hepatocyte low‐density lipoprotein receptor (LDLR), ApoER2, and very low‐density lipoprotein receptor. Because the LDLR is suspected to be involved in hepatitis C virus (HCV) entry, we also tested whether PCSK9 can affect the levels of CD81, a major HCV receptor.

Protein or amino acid deprivation differentially regulates the hepatic forkhead box protein A (FOXA) genes through an activating transcription factor‐4–independent pathway

Nan Su, Michelle M. Thiaville, Keytam Awad, Altin Gjymishka, Jason O. Brant, Thomas P. Yang, Michael S. Kilberg – 23 June 2009 – The FOXA (forkhead box A) proteins (FOXA1, FOXA2, and FOXA3) play a critical role in the development of the liver, and they also regulate metabolism in adult hepatic tissue. The liver responds to changes in nutrient availability by initiating a number of stress signaling pathways. The present studies demonstrated that in mouse dams fed a low‐protein diet hepatic expression of FOXA2 and FOXA3 messenger RNA, but not FOXA1, was induced.

Hepatitis B and C virus coinfection: A novel model system reveals the absence of direct viral interference

Pantxika Bellecave, Jérôme Gouttenoire, Markus Gajer, Volker Brass, George Koutsoudakis, Hubert E. Blum, Ralf Bartenschlager, Michael Nassal, Darius Moradpour – 23 June 2009 – Coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) has been associated with severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests reciprocal replicative suppression of the two viruses, or viral interference. However, interactions between HBV and HCV have been difficult to study due to the lack of appropriate model systems.

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