Osteopontin is a novel downstream target of SOX9 with diagnostic implications for progression of liver fibrosis in humans

James Pritchett, Emma Harvey, Varinder Athwal, Andrew Berry, Cliff Rowe, Fiona Oakley, Anna Moles, Derek A. Mann, Nicoletta Bobola, Andrew D. Sharrocks, Brian J. Thomson, Abed M. Zaitoun, William L. Irving, Indra N. Guha, Neil A. Hanley, Karen Piper Hanley – 5 April 2012 – Osteopontin (OPN) is an important component of the extracellular matrix (ECM), which promotes liver fibrosis and has been described as a biomarker for its severity.

Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation

Maria Jesus Perugorria, Caroline L. Wilson, Mujdat Zeybel, Meagan Walsh, Shilu Amin, Stuart Robinson, Steven A. White, Alastair D. Burt, Fiona Oakley, Hidekazu Tsukamoto, Derek A. Mann, Jelena Mann – 4 April 2012 – Transdifferentiation of hepatic stellate cells (HSCs) to a myofibroblast‐like phenotype is the pivotal event in liver fibrosis. The dramatic change in phenotype associated with transdifferentiation is underpinned by a global change in gene expression.

Distinct contribution of human cord blood‐derived endothelial colony forming cells to liver and gut in a fetal sheep model

Joshua A. Wood, Evan Colletti, Laura E. Mead, David Ingram, Christopher D. Porada, Esmail D. Zanjani, Mervin C. Yoder, Graça Almeida‐Porada – 4 April 2012 – Although the vasculogenic potential of circulating and cord blood (CB)‐derived endothelial colony‐forming cells (ECFC) has been demonstrated in vitro and in vivo, little is known about the inherent biologic ability of these cells to home to different organs and contribute to tissue‐specific cell populations.

Vaniprevir with pegylated interferon alpha‐2a and ribavirin in treatment‐naïve patients with chronic hepatitis C: A randomized phase II study

Michael P. Manns, Edward Gane, Maribel Rodriguez‐Torres, Albrecht Stoehr, Chau‐Ting Yeh, Patrick Marcellin, Richard T. Wiedmann, Peggy M. Hwang, Luzelena Caro, Richard J.O. Barnard, Andrew W. Lee, for the MK‐7009 Protocol 007 Study Group – 2 April 2012 – Vaniprevir (MK‐7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha‐2a (Peg‐IFN‐α‐2a) plus ribavirin (RBV).

Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions

Andreas E. Kremer, Remco van Dijk, Pamela Leckie, Frank G. Schaap, Edith M.M. Kuiper, Thomas Mettang, Katrin S. Reiners, Ulrike Raap, Henk R. van Buuren, Karel J. van Erpecum, Nathan A. Davies, Christian Rust, Andreas Engert, Rajiv Jalan, Ronald P.J. Oude Elferink, Ulrich Beuers – 2 April 2012 – Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus.

Interleukin‐22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice

Xiaoni Kong, Dechun Feng, Hua Wang, Feng Hong, Adeline Bertola, Fu‐Sheng Wang, Bin Gao – 2 April 2012 – Interleukin (IL)‐22 is known to play a key role in promoting antimicrobial immunity, inflammation, and tissue repair at barrier surfaces by binding to the receptors, IL‐10R2 and IL‐22R1. IL‐22R1 is generally thought to be expressed exclusively in epithelial cells. In this study, we identified high levels of IL‐10R2 and IL‐22R1 expression on hepatic stellate cells (HSCs), the predominant cell type involved in liver fibrogenesis in response to liver damage.

Hepatic vein arrival time as assessed by contrast‐enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis

Moon Young Kim, Ki Tae Suk, Soon Koo Baik, Hyoun A. Kim, Young Ju Kim, Seung Hwan Cha, Hwa Ryun Kwak, Mee Yon Cho, Hong Jun Park, Hyo Keun Jeon, So Yeon Park, Bo Ra Kim, Jin Heon Hong, Ki Won Jo, Jae Woo Kim, Hyun Soo Kim, Sang Ok Kwon, Sei Jin Chang, Gwang Ho Baik, Dong Joon Kim – 2 April 2012 – The measurement of the hepatic venous pressure gradient (HVPG) for the estimation of portal hypertension (PH) in cirrhosis has some limitations, including its invasiveness.

Hepatitis B virus X protein stabilizes amplified in breast cancer 1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness

Yonghong Liu, Zhangwei Tong, Ting Li, Qiang Chen, Luting Zhuo, Wengang Li, Ray‐Chang Wu, Chundong Yu – 2 April 2012 – Chronic infection of hepatitis B virus (HBV) is closely associated with the development of human hepatocellular carcinoma (HCC). HBV X protein (HBx) plays a key role in the progression of HCC. We recently found that amplified in breast cancer 1 (AIB1) protein is overexpressed in 68% of human HCC specimens and promotes HCC progression by enhancing cell proliferation and invasiveness.

Liver tumorigenicity promoted by microRNA‐221 in a mouse transgenic model

Elisa Callegari, Bahaeldin K. Elamin, Ferdinando Giannone, Maddalena Milazzo, Giuseppe Altavilla, Francesca Fornari, Luciano Giacomelli, Lucilla D'Abundo, Manuela Ferracin, Cristian Bassi, Barbara Zagatti, Fabio Corrà, Elena Miotto, Laura Lupini, Luigi Bolondi, Laura Gramantieri, Carlo M. Croce, Silvia Sabbioni, Massimo Negrini – 2 April 2012 – MicroRNA‐221 (miR‐221) is one of the most frequently and consistently up‐regulated microRNAs (miRNAs) in human cancer. It has been hypothesized that miR‐221 may act as a tumor promoter.

Ferroportin1 in hepatocytes and macrophages is required for the efficient mobilization of body iron stores in mice

Zhuzhen Zhang, Fan Zhang, Xin Guo, Peng An, Yunlong Tao, Fudi Wang – 2 April 2012 – The liver is a major site of iron storage where sequestered iron can be actively mobilized for utilization when needed elsewhere in the body. Currently, hepatocyte iron efflux mechanisms and their relationships to macrophage iron recycling during the control of whole‐body iron homeostasis are unclear. We hypothesized that the iron exporter, ferroportin1 (Fpn1), is critical for both iron mobilization from hepatocytes and iron recycling from macrophages.

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