Epigenetic regulation of connective tissue growth factor by MicroRNA‐214 delivery in exosomes from mouse or human hepatic stellate cells

Li Chen, Alyssa Charrier, Yu Zhou, Ruju Chen, Bo Yu, Kitty Agarwal, Hidekazu Tsukamoto, L. James Lee, Michael E. Paulaitis, David R. Brigstock – 3 October 2013 – Connective tissue growth factor (CCN2) drives fibrogenesis in hepatic stellate cells (HSC). Here we show that CCN2 up‐regulation in fibrotic or steatotic livers, or in culture‐activated or ethanol‐treated primary mouse HSC, is associated with a reciprocal down‐regulation of microRNA‐214 (miR‐214).

Novel Death Defying Domain in met entraps the active site of caspase‐3 and blocks apoptosis in hepatocytes

Jihong Ma, Chunbin Zou, Lida Guo, Danushka S. Seneviratne, Xinping Tan, Yong‐Kook Kwon, Jiyan An, Robert Bowser, Marie C. DeFrances, Reza Zarnegar – 3 October 2013 – Met, the transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF), is known to function as a potent antiapoptotic mediator in normal and neoplastic cells. Herein we report that the intracellular cytoplasmic tail of Met has evolved to harbor a tandem pair of caspase‐3 cleavage sites, which bait, trap, and disable the active site of caspase‐3, thereby blocking the execution of apoptosis.

Simultaneous detection of hepatitis C virus and interferon stimulated gene expression in infected human liver

Stefan Wieland, Zuzanna Makowska, Benedetta Campana, Diego Calabrese, Michael T. Dill, Josan Chung, Francis V. Chisari, Markus H. Heim – 3 October 2013 – Approximately 50% of patients with chronic hepatitis C (CHC) have ongoing expression of interferon stimulated genes (ISGs) in the liver. It is unclear why this endogenous antiviral response is inefficient in eradicating the infection. Several viral escape strategies have been identified in vitro, including inhibition of interferon (IFN) induction and ISG messenger RNA (mRNA) translation.

Poly (ADP‐ribose) polymerase‐1 is a key mediator of liver inflammation and fibrosis

Partha Mukhopadhyay, Mohanraj Rajesh, Zongxian Cao, Béla Horváth, Ogyi Park, Hua Wang, Katalin Erdelyi, Eileen Holovac, Yuping Wang, Lucas Liaudet, Nabila Hamdaoui, Fouad Lafdil, György Haskó, Csaba Szabo, A. Hamid Boulares, Bin Gao, Pal Pacher – 2 October 2013 – Poly (ADP‐ribose) polymerase 1 (PARP‐1) is a constitutive enzyme, the major isoform of the PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses.

Pulmonary complications in chronic liver disease

Victor I. Machicao, Maya Balakrishnan, Michael B. Fallon – 2 October 2013 – The association of chronic liver disease with respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease have been characterized: hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH). The development of portal hypertension is fundamental in the pathogenesis of each of these disorders.

IL‐17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice

Isaac T.W. Harley, Traci E. Stankiewicz, Daniel A. Giles, Samir Softic, Leah M. Flick, Monica Cappelletti, Rachel Sheridan, Stavra A. Xanthakos, Kris A. Steinbrecher, R. Balfour Sartor, Rohit Kohli, Christopher L. Karp, Senad Divanovic – 2 October 2013 – Inflammation plays a central pathogenic role in the pernicious metabolic and end‐organ sequelae of obesity. Among these sequelae, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the developed world.

Pulmonary complications in chronic liver disease

Victor I. Machicao, Maya Balakrishnan, Michael B. Fallon – 2 October 2013 – The association of chronic liver disease with respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease have been characterized: hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH). The development of portal hypertension is fundamental in the pathogenesis of each of these disorders.

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