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Cholangiocyte hepatocyte

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https://www.readbyqxmd.com/read/29286088/arkadia-protein-expression-is-reduced-in-the-liver-during-the-progression-of-hepatic-fibrosis
#1
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
https://www.readbyqxmd.com/read/29273475/plectin-controls-biliary-tree-architecture-and-stability-in-cholestasis
#2
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
https://www.readbyqxmd.com/read/29248458/hepatic-stem-progenitor-cell-activation-differs-between-primary-sclerosing-and-primary-biliary-cholangitis
#3
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
https://www.readbyqxmd.com/read/29237808/human-fetal-liver-cultures-support-multiple-cell-lineages-that-can-engraft-immunodeficient-mice
#4
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
https://www.readbyqxmd.com/read/29209452/protective-roles-of-hepatic-gaba-signaling-in-liver-injury
#5
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 (GABAARs or GABABRs), in various types of cells. Studies, including ours, show that GABAAR-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
https://www.readbyqxmd.com/read/29207082/autophagy-regulates-proliferation-and-biliary-differentiation-of-hepatic-oval-cells-via-the-mapk-erk-signaling-pathway
#6
Dongdong Chen, Xiaoxiao Wu, Jie Zheng, Ruijie Dai, Zhichao Mo, Fahad Munir, Xiaolong Ni, Yunfeng Shan
Hepatic oval cells (HOCs) are thought to possess self‑renewal ability and a bipotential capacity for differentiation, which allows them to differentiate into hepatocytes and cholangiocytes. Autophagy serves an important role in self‑renewal and differentiation of stem cells; however, how autophagy contributes to proliferation and differentiation of hepatic progenitor cells has yet to be elucidated. In the present study, autophagy was regulated by rapamycin (Rapa) and chloroquine (Chlo) administration. The results demonstrated that Chlo‑treated HOCs exhibited decreased autophagic activity alongside a decreased tendency to proliferate, as determined by Cell Counting Kit‑8...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29180269/dysregulation-of-antioxidant-responses-in-patients-diagnosed-with-concomitant-primary-sclerosing-cholangitis-inflammatory-bowel-disease
#7
Colin T Shearn, David J Orlicky, Dennis R Petersen
OBJECTIVE: Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease that is characterized by severe peri-biliary tract inflammation and fibrosis, elevated oxidative stress and hepatocellular injury. A hallmark of PSC patients is the concurrent diagnosis of Inflammatory Bowel Disease occurring in approximately 70%-80% of PSC patients (PSC/IBD). The objective of this study was to determine the impact of end stage PSC/IBD on cellular antioxidant responses and the formation of protein carbonylation...
November 24, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29170436/fate-tracing-of-hepatocytes-in-mouse-liver
#8
Xiaowen Gu, Danyi Huang, Lei Ci, Jiahao Shi, Mengjie Zhang, Hua Yang, Zhugang Wang, Zhejin Sheng, Ruilin Sun, Jian Fei
Hepatocytes perform most of the functions of the liver and are considered terminally differentiated cells. Recently, it has been suggested that hepatocytes might have the potential to transdifferentiate or dedifferentiate under physiological or pathological conditions in vivo. Epithelial-mesenchymal transition of hepatocytes in liver fibrosis has also been proposed. However, these findings have not been fully confirmed. In this study, hepatocytes were genetically labelled for cell fate tracing using lacZ via the tamoxifen-induced CreERT/loxP system...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29154966/determinants-of-fibrosis-progression-and-regression-in-nash
#9
REVIEW
Detlef Schuppan, Rambabu Surabattula, Xiao Yu Wang
Cirrhosis has become the major liver related clinical endpoint in nonalcoholic steatohepatitis. However, progression to cirrhosis is less predictable in NASH compared to other chronic liver diseases. This is due to the complex and multifactorial etiology of NASH, which is determined by life style and nutrition, multiple genetic and epigenetic factors, and a prominent role of hepatic and extrahepatic comorbidities. Thus modest changes in these cofactors can also induce fibrosis regression, at least in precirrhotic patients...
November 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29154784/tgf-%C3%AE-1-signaling-regulates-mouse-hepatic-stellate-cell-differentiation-via-the-jagged1-notch-pathway
#10
Yasen Aimaiti, Xin Jin, Wei Wang, Zixin Chen, Dewei Li
AIMS: We tested whether transforming growth factor β1 (TGF-β1) signaling plays an important role in hepatic stellate cell differentiation fate and investigated the role of Jagged1/Notch in this process. MATERIALS AND METHODS: TGF-β1 was overexpressed and transforming growth factor receptor 1 (TGF-β-R1) was knocked down by a lentiviral vector in mouse hepatic stellate cells (mHSCs). Transfection efficiency was assessed with immunofluorescence, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and western blotting...
November 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/29149928/rheumatic-manifestations-in-autoimmune-liver-disease
#11
REVIEW
Carlo Selmi, Elena Generali, Merrill Eric Gershwin
Autoimmune liver diseases coexist with rheumatic disorders in approximately 30% of cases and may also share pathogenic mechanisms. Autoimmune liver diseases result from an immune-mediated injury of different tissues, with autoimmune hepatitis (AIH) targeting hepatocytes, and primary biliary cholangitis (PBC) and primary sclerosing cholangitis targeting cholangiocytes. Sjogren syndrome is diagnosed in 7% of AIH cases and serologic autoimmunity profiles are a common laboratory abnormality, particularly in the case of serum antimitochondrial (PBC) or anti-liver kidney microsomal antibodies (AIH)...
February 2018: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/29116012/connexin-32-and-connexin-43-are-involved-in-lineage-restriction-of-hepatic-progenitor-cells-to-hepatocytes
#12
Haiyun Pei, Chao Zhai, Huilin Li, Fang Yan, Jinhua Qin, Hongfeng Yuan, Rui Zhang, Shuyong Wang, Wencheng Zhang, Mingyang Chang, Yunfang Wang, Xuetao Pei
BACKGROUND: Bi-potential hepatic progenitor cells can give rise to both hepatocytes and cholangiocytes, which is the last phase and critical juncture in terms of sequentially hepatic lineage restriction from any kind of stem cells. If their differentiation can be controlled, it might access to functional hepatocytes to develop pharmaceutical and biotechnology industries as well as cell therapies for end-stage liver diseases. METHODS: In this study, we investigated the influence of Cx32 and Cx43 on hepatocyte differentiation of WB-F344 cells by in vitro gain and loss of function analyses...
November 7, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29100373/chronically-high-level-of-tgfb1a-induction-causes-both-hepatocellular-carcinoma-and-cholangiocarcinoma-via-a-dominant-erk-pathway-in-zebrafish
#13
Chuan Yan, Qiqi Yang, Han-Ming Shen, Jan M Spitsbergen, Zhiyuan Gong
Liver cancers including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) have increased steadily with the prevalence of non-alcoholic steatohepatitis (NASH), but the underlying mechanism for the transition from NASH to liver cancers remains unclear. Here we first employed diet-induced NASH zebrafish and found that elevated level of satiety hormone, leptin, induced overexpression of tgfb1. Then we developed tgfb1a transgenic zebrafish for inducible, hepatocyte-specific expression. Interestingly, chronically high tgfb1a induction in hepatocytes could concurrently drive both HCC and CCA...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29095436/rna-sequencing-based-comparative-analysis-of-human-hepatic-progenitor-cells-and-their-niche-from-alcoholic-steatohepatitis-livers
#14
An Ceulemans, Stefaan Verhulst, Matthias Van Haele, Olivier Govaere, Juan-Jose Ventura, Leo A van Grunsven, Tania Roskams
Hepatic progenitor cells (HPCs) are small cells with a relative large oval nucleus and a scanty cytoplasm situated in the canals of Hering that express markers of (immature) hepatocytes and cholangiocytes. HPCs are present in large numbers in alcoholic steatohepatitis (ASH), one of the leading causes of chronic liver disease. To date, the mechanisms responsible for proliferation and differentiation of human HPCs are still poorly understood and the role of HPCs in ASH development is unknown. In this study, we aimed to characterise human HPCs and their interactions with other cells through comparison, on both protein and RNA level, of HPC-enriched cell populations from adult human liver tissue using different isolation methods...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29080340/bile-acids-in-cholestasis-and-its-treatment
#15
Juan Pablo Arab, Daniel Cabrera, Marco Arrese
Bile acids (BA) are key molecules in generating bile flow, which is an essential function of the liver. In the last decades there have been great advances in the understanding of the role of a number of specific transport proteins present at the sinusoidal and canalicular membrane domains of hepatocytes and cholangiocytes in generating and maintaining bile flow. Also, a clearer understanding on how BA regulate their own synthesis and the expression and/or function of transporters has been reached. This new knowledge has helped to better delineate the pathophysiology of cholestasis and the adaptive responses of hepatocytes to cholestatic liver injury as well as of the mechanisms of injury of biliary epithelia...
October 28, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29067165/recent-advances-in-understanding-cholangiocarcinoma
#16
REVIEW
Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Nicole Francis, Rowan Seils, Sara Villamaria, Heather Francis
Cholangiocarcinoma (CCA) is an aggressive malignancy that arises from damaged epithelial cells, cholangiocytes, and possibly de-differentiated hepatocytes. CCA has a poor overall survival rate and limited therapeutic options. Based on this data, it is imperative that new diagnostic and therapeutic interventions be developed. Recent work has attempted to understand the pathological mechanisms driving CCA progression. Specifically, recent publications have delved into the role of cancer stem cells (CSCs), mesenchymal stem cells (MSCs), and microRNAs (miRNAs) during CCA pathology...
2017: F1000Research
https://www.readbyqxmd.com/read/29017397/liver-scaffolds-support-survival-and-metabolic-function-of-multilineage-neonatal-allogenic-cells
#17
Wessam Hassanein, Arielle Cimeno, Avraham Werdesheim, Bryan Buckingham, Joshua Harrison, Mehmet C Uluer, Ali Khalifeh, Carlos Rivera-Pratts, Stephen Klepfer, Jhade D Woodall, Urmil Dhru, Elliot Bromberg, Dawn Parsell, Cinthia Drachenberg, Rolf N Barth, John C LaMattina
Organ scaffold bioengineering is currently limited by the inability to effectively repopulate the scaffold with appropriately distributed functional cells. We examined the feasibility of a decellularized liver scaffold to support the growth and function of multilineage allogenic cells derived from either adult or neonatal liver cells. Cell slurries from neonatal and adult rat livers containing hepatocytes, cholangiocytes, and endothelial cells were introduced into decellularized adult rat liver scaffolds via the bile duct...
October 10, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28951464/proliferating-epcam-positive-ductal-cells-in-the-inflamed-liver-give-rise-to-hepatocellular-carcinoma
#18
Tomonori Matsumoto, Atsushi Takai, Yuji Eso, Kazuo Kinoshita, Toshiaki Manabe, Hiroshi Seno, Tsutomu Chiba, Hiroyuki Marusawa
Hepatocellular carcinoma (HCC) originates from regenerating liver cells with genetic alterations in chronically inflamed liver. Ductal cells and hepatocytes proliferate for liver regeneration, and proliferating ductal cells (PDC) derived from bile ductules have long been considered putative liver stem/progenitor cells and candidate cellular origins of HCC. The potential of PDC as tumor-originating cells, however, remains controversial in contrast to accumulating evidence that HCC originates from hepatocytes...
September 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28935574/taurocholate-induces-biliary-differentiation-of-liver-progenitor-cells-causing-hepatic-stellate-cell-chemotaxis-in-the-ductular-reaction-role-in-pediatric-cystic-fibrosis-liver-disease
#19
Katarzyna N Pozniak, Michael A Pearen, Tamara N Pereira, Cynthia S M Kramer, Priyakshi Kalita-De Croft, Sujeevi K Nawaratna, Manuel A Fernandez-Rojo, Geoffrey N Gobert, Janina E E Tirnitz-Parker, John K Olynyk, Ross W Shepherd, Peter J Lewindon, Grant A Ramm
Cystic fibrosis liver disease (CFLD) in children causes progressive fibrosis leading to biliary cirrhosis; however, its cause(s) and early pathogenesis are unclear. We hypothesized that a bile acid-induced ductular reaction (DR) drives fibrogenesis. The DR was evaluated by cytokeratin-7 immunohistochemistry in liver biopsies, staged for fibrosis, from 60 children with CFLD, and it demonstrated that the DR was significantly correlated with hepatic fibrosis stage and biliary taurocholate levels. To examine the mechanisms involved in DR induction, liver progenitor cells (LPCs) were treated with taurocholate, and key events in DR evolution were assessed: LPC proliferation, LPC biliary differentiation, and hepatic stellate cell (HSC) chemotaxis...
September 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28923495/crispr-cas9-engineering-of-adult-mouse-liver-demonstrates-that-the-dnajb1-prkaca-gene-fusion-is-sufficient-to-induce-tumors-resembling-fibrolamellar-hepatocellular-carcinoma
#20
Lars H Engelholm, Anjum Riaz, Denise Serra, Frederik Dagnæs-Hansen, Jens V Johansen, Eric Santoni-Rugiu, Steen H Hansen, Francesco Niola, Morten Frödin
BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis...
September 18, 2017: Gastroenterology
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