Cholangiocyte‐derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans

Xiaojiaoyang Li, Runping Liu, Zhiming Huang, Emily C. Gurley, Xuan Wang, Juan Wang, Hongliang He, Hu Yang, Guanhua Lai, Luyong Zhang, Jasmohan S. Bajaj, Melanie White, William M. Pandak, Phillip B. Hylemon, Huiping Zhou – 9 February 2018 – Cholestatic liver injury is an important clinical problem with limited understanding of disease pathologies. Exosomes are small extracellular vesicles released by a variety of cells, including cholangiocytes.

Resistance analysis of genotype 3 hepatitis C virus indicates subtypes inherently resistant to nonstructural protein 5A inhibitors

David Smith, Andrea Magri, David Bonsall, Camilla L.C. Ip, Amy Trebes, Anthony Brown, Palo Piazza, Rory Bowden, Dung Nguyen, M. Azim Ansari, Peter Simmonds, Eleanor Barnes, STOP‐HCV Consortium – 9 February 2018 – Hepatitis C virus (HCV) genotype (gt) 3 is highly prevalent globally, with non‐gt3a subtypes common in Southeast Asia. Resistance‐associated substitutions (RASs) have been shown to play a role in treatment failure. However, the role of RASs in gt3 is not well understood.

Vinyl chloride dysregulates metabolic homeostasis and enhances diet‐induced liver injury in mice

Anna L. Lang, Liya Chen, Gavin D. Poff, Wen‐Xing Ding, Russel A. Barnett, Gavin E. Arteel, Juliane I. Beier – 9 February 2018 – Vinyl chloride (VC), a common industrial organochlorine and environmental pollutant, has been shown to directly cause hepatic angiosarcoma and toxicant‐associated steatohepatitis at high exposure levels. However, the impact of lower concentrations of VC on the progression of underlying liver diseases (e.g., nonalcoholic fatty liver disease [NAFLD]) is unclear.

Endothelial Notch activation reshapes the angiocrine of sinusoidal endothelia to aggravate liver fibrosis and blunt regeneration in mice

Juan‐Li Duan, Bai Ruan, Xian‐Chun Yan, Liang Liang, Ping Song, Zi‐Yan Yang, Yuan Liu, Ke‐Feng Dou, Hua Han, Lin Wang – 8 February 2018 – Liver sinusoidal endothelial cells (LSECs) critically regulate liver homeostasis and diseases through angiocrine factors. Notch is critical in endothelial cells (ECs). In the current study, Notch signaling was activated by inducible EC‐specific expression of the Notch intracellular domain (NIC). We found that endothelial Notch activation damaged liver homeostasis.

Expression of microRNA‐155 in inflammatory cells modulates liver injury

Delia Blaya, Beatriz Aguilar‐Bravo, Fengjie Hao, Silvia Casacuberta‐Serra, Mar Coll, Luis Perea, Júlia Vallverdú, Isabel Graupera, Elisa Pose, Laura Llovet, Jordi Barquinero, Francisco Javier Cubero, Juan Caballería, Pere Ginès, Pau Sancho‐Bru – 8 February 2018 – MicroRNA 155 (miR‐155) is involved in immune and inflammatory diseases and is associated with liver fibrosis and steatohepatitis. However, the mechanisms involved in miR‐155 regulation of liver injury are largely unknown.

MicroRNA (miR)‐433 and miR‐22 dysregulations induce histone‐deacetylase‐6 overexpression and ciliary loss in cholangiocarcinoma

Adrian P. Mansini, Maria J. Lorenzo Pisarello, Kristen M. Thelen, Maetzin Cruz‐Reyes, Estanislao Peixoto, Sujeong Jin, Brynn N. Howard, Christy E. Trussoni, Gabriella B. Gajdos, Nicholas F. LaRusso, Maria J. Perugorria, Jesus M. Banales, Sergio A. Gradilone – 6 February 2018 – Cholangiocytes normally express primary cilia, a multisensory organelle that detects signals from the cellular environment. Cilia are significantly reduced in cholangiocarcinoma (CCA) by a mechanism involving overexpression of histone deacetylase 6 (HDAC6).

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