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Cholangiocyte hepatocyte

Jingxiao Wang, Mingjie Dong, Zhong Xu, Xinhua Song, Shanshan Zhang, Yu Qiao, Li Che, John Gordan, Kaiwen Hu, Yan Liu, Diego F Calvisi, Xin Chen
Liver cancer comprises a group of malignant tumors, among which hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common. ICC is especially pernicious and associated with poor clinical outcome. Studies have shown that a subset of human ICCs may originate from mature hepatocytes. However, the mechanisms driving the trans-differentiation of hepatocytes into malignant cholangiocytes remain poorly defined. We adopted lineage tracing techniques and an established murine hepatocyte-derived ICC model by hydrodynamic injection of activated forms of AKT (myr-AKT) and Yap (YapS127A) proto-oncogenes...
March 16, 2018: Oncogene
Jacquelyn O Russell, Sungjin Ko, Harvinder S Saggi, Sucha Singh, Minakshi Poddar, Donghun Shin, Satdarshan P Monga
Bromodomain and extraterminal (BET) proteins recruit key components of basic transcriptional machinery to promote gene expression. Aberrant expression and mutations in BET genes have been identified in many malignancies. Small molecule inhibitors of BET proteins like JQ1 have shown efficacy in preclinical cancer models including affecting growth of hepatocellular carcinoma. BET proteins also regulate cell proliferation in nontumor settings. We recently showed that BET proteins regulate cholangiocyte-driven liver regeneration...
March 12, 2018: American Journal of Pathology
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
Alexander Raven, Wei-Yu Lu, Tak Yung Man, Sofia Ferreira-Gonzalez, Eoghan O'Duibhir, Benjamin J Dwyer, John P Thomson, Richard R Meehan, Roman Bogorad, Victor Koteliansky, Yuri Kotelevtsev, Charles Ffrench-Constant, Luke Boulter, Stuart J Forbes
This corrects the article DOI: 10.1038/nature23015.
March 14, 2018: Nature
Andrey Elchaninov, Timur Fatkhudinov, Natalia Usman, Irina Arutyunyan, Andrey Makarov, Anastasia Lokhonina, Irina Eremina, Viktor Surovtsev, Dmitry Goldshtein, Galina Bolshakova, Valeria Glinkina, Gennady Sukhikh
AIM: To investigate the influence of the umbilical cord-derived multipotent stromal cells (MSCs) on recovery of the liver after the subtotal resection, that is, removal of 80% of the organ mass, a renowned model of the small-for-size liver remnant syndrome. METHODS: The MSCs were obtained from the intervascular tissue of umbilical cords, dissected from rat fetuses, by the explant culture technique. The vital labeling of MSCs with РКН26 was carried out on the 3rd passage...
February 27, 2018: World Journal of Hepatology
Yi Shi, Jianfeng Bai, Shuwei Guo, Jiandong Wang
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy of the bile duct, representing the second most common primary liver cancer. Wntless (Wls) is a highly conserved transmembrane protein that shuttles palmitoylated Wnt proteins from the endoplasmic reticulum to the plasma membrane. Wls is highly expressed in various types of cancers and is essential for cell proliferation, anti-apoptotic activity, and survival. The profile of Wls expression and its clinical significance has not been well clarified in ICC...
2018: Tohoku Journal of Experimental Medicine
Sofia Ferreira-Gonzalez, Wei-Yu Lu, Alexander Raven, Benjamin Dwyer, Tak Yung Man, Eoghan O'Duibhir, Philip J Starkey Lewis, Lara Campana, Tim J Kendall, Thomas G Bird, Nuria Tarrats, Juan-Carlos Acosta, Luke Boulter, Stuart J Forbes
Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression to prevent undesired proliferation. However, under pathological circumstances, senescence can adversely affect organ function, viability and regeneration. We have developed a mouse model of biliary senescence, based on the conditional deletion of Mdm2 in bile ducts under the control of the Krt19 promoter, that exhibits features of biliary disease. Here we report that senescent cholangiocytes induce profound alterations in the cellular and signalling microenvironment, with recruitment of myofibroblasts and macrophages causing collagen deposition, TGFβ production and induction of senescence in surrounding cholangiocytes and hepatocytes...
March 9, 2018: Nature Communications
Francesca Maione, Nicholas Gilbo, Silvia Lazzaro, Peter Friend, Giovanni Camussi, Renato Romagnoli, Jacques Pirenne, Ina Jochmans, Diethard Monbaliu
BACKGROUND: Understanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated. METHODS: We systematically reviewed the current experimental set-ups for ILP and parameters of interest reflecting IRI. RESULTS: ILP was never compared to transplantation in animals...
March 5, 2018: Transplantation
Cinthya Santos Cirqueira, Aloisio Sousa Felipe-Silva, Alda Wakamatsu, Lidiane Vieira Marins, Eziel Cavalcanti Rocha, Evandro Sobroza de Mello, Venâncio Avancini Ferreira Alves
Multidrug resistance-associated protein 2 (MRP2) is a multi-specific organic anion transporter predominantly expressed in the canalicular membrane of hepatocytes, epithelial cells from gallbladder and apical membranes of proximal tubular kidney epithelium whereas multidrug resistance-associated protein 3 (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes. This study aims to detect the expression of these transporters in hepatocellular carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for future studies on differential diagnosis and on clinical essays...
February 20, 2018: Pathology Oncology Research: POR
Yoshimasa Saito, Toshiaki Nakaoka, Toshihide Muramatsu, Hidenori Ojima, Aoi Sukeda, Yuko Sugiyama, Ryoei Uchida, Ryo Furukawa, Aya Kitahara, Toshiro Sato, Yae Kanai, Hidetsugu Saito
Intrahepatic cholangiocarcinoma (IHCC) is a highly aggressive malignancy with a poor prognosis. It is thought to originate from cholangiocytes, which are the component cells of intrahepatic bile ducts. However, as patients with viral hepatitis often develop IHCC, it has been suggested that transformed hepatocytes may play a role in IHCC development. To investigate whether IHCC cells can be converted to functional hepatocytes, we established organoids derived from human IHCC and cultured them under conditions suitable for hepatocyte differentiation...
February 12, 2018: Scientific Reports
Xiang Jiang, Min Lian, Yanmei Li, Weici Zhang, Qixia Wang, Yiran Wei, Jun Zhang, Weihua Chen, Xiao Xiao, Qi Miao, Zhaolian Bian, Dekai Qiu, Jingyuan Fang, Aftab A Ansari, Patrick S C Leung, Ross L Coppel, Ruqi Tang, M Eric Gershwin, Xiong Ma
Mucosal-associated invariant T (MAIT) cells are novel innate-like T cells constituting a significant proportion of circulating and hepatic T cells. Herein, we extensively examine the phenotypical and functional alterations of MAIT cells and their regulation in a cohort of 56 patients with Primary Biliary Cholangitis (PBC) and 53 healthy controls (HC). Additionally alterations of MAIT cells were assessed before and after UDCA treatment. Finally the localization of MAIT cell in liver was examined using specific tetramer staining and the underlying mechanisms of these alterations in PBC were explored...
February 8, 2018: Journal of Autoimmunity
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
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. Exosome-mediated cell-cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies indicate that the long non-coding RNA H19 is mainly expressed in cholangiocytes and its aberrant expression is associated with significant down-regulation of small heterodimer partner (SHP) in hepatocytes and cholestatic liver injury in multidrug resistance 2 knockout (Mdr2-/- ) mice...
February 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ran-Ran Zhang, Yun-Wen Zheng, Bin Li, Yun-Zhong Nie, Yasuharu Ueno, Tomonori Tsuchida, Hideki Taniguchi
BACKGROUND: Mature human hepatocytes are critical in preclinical research and therapy for liver disease, but are difficult to manipulate and expand in vitro. Hepatic stem cells (HpSCs) may be an alternative source of functional hepatocytes for cell therapy and disease modeling. Since these cells play an import role in regenerative medicine, the precise characterization that determines specific markers used to isolate these cells as well as whether they contribute to liver regeneration still remain to be shown...
February 5, 2018: Stem Cell Research & Therapy
Tea Soini, Marjut Pihlajoki, Noora Andersson, Jouko Lohi, Kari A Huppert, David A Rudnick, Stacey S Huppert, David B Wilson, Mikko P Pakarinen, Markku Heikinheimo
Biliary atresia (BA), a neonatal liver disease, is characterized by obstruction of extrahepatic bile ducts with subsequent cholestasis, inflammation, and progressive liver fibrosis. To gain insights into the pathophysiology of BA, we focused attention on GATA6, a transcription factor implicated in biliary development. Early in fetal development GATA6 expression is evident in cholangiocytes and hepatocytes, but by late gestation it is extinguished in hepatocytes. Utilizing a unique set of BA liver samples collected before and after successful portoenterostomy (PE), we found that GATA6 expression is markedly upregulated in hepatocytes of patients with BA compared to healthy and cholestatic disease controls...
February 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Elizabeth Brunt, Shinichi Aishima, Pierre-Alain Clavien, Kathryn Fowler, Zachary Goodman, Gregory Gores, Annette Gouw, Alex Kagen, David Klimstra, Mina Komuta, Fukuo Kondo, Rebecca Miksad, Masayuki Nakano, Yasuni Nakanuma, Irene Ng, Valerie Paradis, Young Nyun Park, Alberto Quaglia, Massimo Roncalli, Tania Roskams, Michiie Sakamoto, Romil Saxena, Christine Sempoux, Claude Sirlin, Ashley Stueck, Swan Thung, W M S Tsui, Xin-Wei Wang, Aileen Wee, Hirohisa Yano, Matthew Yeh, Yoh Zen, Jessica Zucman-Rossi, Neil Theise
Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, due to lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue...
January 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Fei Hou, Ruixia Liu, Xiaoya Liu, Lijian Cui, Xiaozheng Yu, Yan Wen, Huiguo Ding, Chenghong Yin
Arkadia is able to degrade key signaling molecules in the transforming growth factor (TGF)‑β1 signaling pathway; however, the expression of Arkadia in the liver during development and progression of TGF‑β1/Smad signaling‑regulated hepatic fibrosis remains to be elucidated. The present study aimed to examine Arkadia expression in the livers of two rat models of hepatic fibrosis induced by bile duct ligation and carbon tetrachloride intoxication, and in human liver samples from patients with hepatic fibrosis...
December 22, 2017: International Journal of Molecular Medicine
Marketa Jirouskova, Katerina Nepomucka, Gizem Oyman-Eyrilmez, Alzbeta Kalendova, Helena Havelkova, Lenka Sarnova, Karel Chalupsky, Bjoern Schuster, Oldrich Benada, Petra Miksatkova, Martin Kuchar, Ondrej Fabian, Radislav Sedlacek, Gerhard Wiche, Martin Gregor
BACKGROUND & AIMS: Plectin, a highly versatile cytolinker protein, controls intermediate filament (IF) cytoarchitecture and cellular stress response. In the present study, we investigate the role of plectin in the liver under basal conditions and in experimental cholestasis. METHODS: We generated liver-specific Plectin knockout (PleΔalb) mice and analyzed them using two cholestatic liver injury models: bile duct ligation (BDL) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding...
December 19, 2017: Journal of Hepatology
Guido Carpino, Vincenzo Cardinale, Trine Folseraas, Diletta Overi, Annarosa Floreani, Antonio Franchitto, Paolo Onori, Nora Cazzagon, Pasquale Bartolomeo Berloco, Tom Hemming Karlsen, Domenico Alvaro, Eugenio Gaudio
Primary sclerosing cholangitis and primary biliary cholangitis are human primary cholangiopathies; these diseases are characterized by the damage of mature cholangiocytes and by the appearance of ductular reaction as the results of hepatic progenitor cell activation. The aims of this study were to evaluate differences in progenitor cell niche activation between these two human cholangiopathies. Human liver tissue was obtained from normal liver donors (n=5), primary sclerosing (n=20), and primary biliary cholangitis (n=20)...
December 14, 2017: American Journal of Pathology
Marina E Fomin, Ashley I Beyer, Marcus O Muench
During prenatal development the liver is composed of multiple cell types with unique properties compared to their adult counterparts. We aimed to establish multilineage cultures of human fetal liver cells that could maintain stem cell and progenitor populations found in the developing liver. An aim of this study was to test if maturation of fetal hepatocytes in short-term cultures supported by epidermal growth factor and oncostatin M can improve their ability to engraft immunodeficient mice. Fetal liver cultures supported a mixture of albumin+ cytokertin-19+ hepatoblasts, hepatocytes, cholangiocytes, CD14++CD32+ liver sinusoidal endothelial cells (LSECs) and CD34+CD133+ haematopoietic stem cells...
December 2017: Open Biology
Shuanglian Wang, Lu Zhang, Chuanyong Liu, Wei-Yang Lu
In addition to functioning as a neurotransmitter, γ-aminobutyric acid (GABA) generates signals, via its type A or type B receptors (GABAA Rs or GABAB Rs), in various types of cells. Studies, including ours, show that GABAA R-mediated auto- and paracrine GABAergic signaling occurs in rodent hepatocytes and cholangiocytes, protecting the liver against toxic injuries. This short article briefly introduces the GABA signaling system in rodent livers and discusses potential mechanisms by which the hepatic GABA signaling protects the liver function...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
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