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https://www.readbyqxmd.com/read/29317337/heart-and-bile-acids-clinical-consequences-of-altered-bile-acid-metabolism
#1
REVIEW
Tharni Vasavan, Elisa Ferraro, Effendi Ibrahim, Peter Dixon, Julia Gorelik, Catherine Williamson
Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart...
January 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29286088/arkadia-protein-expression-is-reduced-in-the-liver-during-the-progression-of-hepatic-fibrosis
#2
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
#3
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/29261670/human-intrahepatic-ilc2-are-il-13positive-amphiregulinpositive-and-their-frequency-correlates-with-model-of-end-stage-liver-disease-score
#4
Hannah C Jeffery, Patrick McDowell, Philipp Lutz, Rebecca E Wawman, Sheree Roberts, Chris Bagnall, Jane Birtwistle, David H Adams, Ye Htun Oo
INTRODUCTION: Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue. METHODS: Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function...
2017: PloS One
https://www.readbyqxmd.com/read/29248461/knockout-of-l-histidine-decarboxylase-hdc-prevents-cholangiocyte-damage-and-hepatic-fibrosis-in-mice-subjected-to-high-fat-diet-feeding-via-disrupted-histamine-leptin-signaling
#5
Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Jennifer Bailey, Wasim Dar, Kishore Polireddy, Qingzheng Chen, Moises I Nevah Rubin, Amelia Sybenga, Sharon DeMorrow, Fanyin Meng, Lindsey Stockton, Gianfranco Alpini, Heather Francis
Administration of a high-fat diet (HFD) coupled with sugar, mimicking a Western diet, causes fatty liver disease in mice. Histamine induces biliary proliferation and fibrosis, and regulates leptin signaling. Wild-type (WT) and l-histidine decarboxylase (Hdc-/-) mice were fed a control diet or a HFD coupled with a high fructose corn syrup equivalent. H&E and Oil Red O staining were performed to determine steatosis. Intrahepatic biliary mass and cholangiocyte proliferation were evaluated by immunohistochemistry...
December 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29248458/hepatic-stem-progenitor-cell-activation-differs-between-primary-sclerosing-and-primary-biliary-cholangitis
#6
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/29243290/a-non-coding-variant-in-ganab-explains-isolated-polycystic-liver-disease-pcld-in-a-large-family
#7
Whitney Besse, Jungmin Choi, Dina Ahram, Shrikant Mane, Simone Sanna-Cherchi, Vicente Torres, Stefan Somlo
Expanded mutation detection and novel gene discovery for isolated polycystic liver disease (PCLD) are necessary as 50% of cases do not have identified mutations in the seven published disease genes. We investigated a family with 5 affected siblings for which no loss of function variants were identified by whole exome sequencing analysis. SNP genotyping and linkage analysis narrowed the candidate regions to ∼8% of the genome, which included two published PCLD genes in close proximity to each other, GANAB and LRP5...
December 15, 2017: Human Mutation
https://www.readbyqxmd.com/read/29237808/human-fetal-liver-cultures-support-multiple-cell-lineages-that-can-engraft-immunodeficient-mice
#8
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/29228347/exposure-of-mice-to-1-2-dichloropropane-induces-cyp450-dependent-proliferation-and-apoptosis-of-cholangiocytes
#9
Xiao Zhang, Cai Zong, Lingyi Zhang, Edwin Garner, Shigeyuki Sugie, Chinyen Huang, Wenting Wu, Jie Chang, Toshihiro Sakurai, Masashi Kato, Sahoko Ichihara, Shinji Kumagai, Gaku Ichihara
1, 2-Dichloropropane (1, 2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to Group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing workers exposed to 1, 2-DCP in Japan. Two-year rodent carcinogenicity bioassays demonstrated that 1, 2-DCP induced tumors in liver and lung, but not in bile duct. The present study was designed to assess the toxic effects of 1, 2-DCP on proliferation and apoptosis in mice bile duct and the role of cytochrome P450 (CYP450) in any such effect...
December 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29209452/protective-roles-of-hepatic-gaba-signaling-in-liver-injury
#10
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
#11
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/29202695/single-cell-rna-seq-analysis-reveals-dynamic-trajectories-during-mouse-liver-development
#12
Xianbin Su, Yi Shi, Xin Zou, Zhao-Ning Lu, Gangcai Xie, Jean Y H Yang, Chong-Chao Wu, Xiao-Fang Cui, Kun-Yan He, Qing Luo, Yu-Lan Qu, Na Wang, Lan Wang, Ze-Guang Han
BACKGROUND: The differentiation and maturation trajectories of fetal liver stem/progenitor cells (LSPCs) are not fully understood at single-cell resolution, and a priori knowledge of limited biomarkers could restrict trajectory tracking. RESULTS: We employed marker-free single-cell RNA-Seq to characterize comprehensive transcriptional profiles of 507 cells randomly selected from seven stages between embryonic day 11.5 and postnatal day 2.5 during mouse liver development, and also 52 Epcam-positive cholangiocytes from postnatal day 3...
December 4, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29180269/dysregulation-of-antioxidant-responses-in-patients-diagnosed-with-concomitant-primary-sclerosing-cholangitis-inflammatory-bowel-disease
#13
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
#14
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/29169115/prolonged-oxidative-stress-down-regulates-early-b-cell-factor-1-with-inhibition-of-its-tumor-suppressive-function-against-cholangiocarcinoma-genesis
#15
Napat Armartmuntree, Mariko Murata, Anchalee Techasen, Puangrat Yongvanit, Watcharin Loilome, Nisana Namwat, Chawalit Pairojkul, Chadamas Sakonsinsiri, Somchai Pinlaor, Raynoo Thanan
Early B cell factor 1 (EBF1) is a transcription factor involved in the differentiation of several stem cell lineages and it is a negative regulator of estrogen receptors. EBF1 is down-regulated in many tumors, and is believed to play suppressive roles in cancer promotion and progression. However, the functional roles of EBF1 in carcinogenesis are unclear. Liver fluke-infection-associated cholangiocarcinoma (CCA) is an oxidative stress-driven cancer of bile duct epithelium. In this study, we investigated EBF1 expression in tissues from CCA patients, CCA cell lines (KKU-213, KKU-214 and KKU-156), cholangiocyte (MMNK1) and its oxidative stress-resistant (ox-MMNK1-L) cell lines...
November 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/29167395/large-scale-proteomics-identifies-mmp-7-as-a-sentinel-of-epithelial-injury-and-of-biliary-atresia
#16
Chatmanee Lertudomphonwanit, Reena Mourya, Lin Fei, Yue Zhang, Sridevi Gutta, Li Yang, Kevin E Bove, Pranavkumar Shivakumar, Jorge A Bezerra
Biliary atresia is a progressive infantile cholangiopathy of complex pathogenesis. Although early diagnosis and surgery are the best predictors of treatment response, current diagnostic approaches are imprecise and time-consuming. We used large-scale, quantitative serum proteomics at the time of diagnosis of biliary atresia and other cholestatic syndromes (serving as disease controls) to identify biomarkers of disease. In a discovery cohort of 70 subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which retained high distinguishing features for biliary atresia in two validation cohorts...
November 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29162437/mouse-model-of-alagille-syndrome-and-mechanisms-of-jagged1-missense-mutations
#17
Emma R Andersson, Indira V Chivukula, Simona Hankeova, Marika Sjöqvist, Yat Long Tsoi, Daniel Ramsköld, Jan Masek, Aiman Elmansuri, Anita Hoogendoorn, Elenae Vazquez, Helena Storvall, Julie Netušilová, Meritxell Huch, Björn Fischler, Ewa Ellis, Adriana Contreras, Antal Nemeth, Kenneth C Chien, Hans Clevers, Rickard Sandberg, Vitezslav Bryja, Urban Lendahl
BACKGROUND & AIMS: Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We aimed to develop a mouse model of Alagille syndrome to elucidate these mechanisms. METHODS: Mice with a missense mutation (H268Q) in Jag1 (Jag1(+)/(Ndr) mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1(Ndr/Ndr) mice)...
November 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29158418/a-novel-pkhd1-mutation-interacts-with-the-nonobese-diabetic-genetic-background-to-cause-autoimmune-cholangitis
#18
Wenting Huang, Daniel B Rainbow, Yuehong Wu, David Adams, Pranavkumar Shivakumar, Leah Kottyan, Rebekah Karns, Bruce Aronow, Jorge Bezerra, M Eric Gershwin, Laurence B Peterson, Linda S Wicker, William M Ridgway
We previously reported that NOD.c3c4 mice develop spontaneous autoimmune biliary disease (ABD) with anti-mitochondrial Abs, histopathological lesions, and autoimmune T lymphocytes similar to human primary biliary cholangitis. In this article, we demonstrate that ABD in NOD.c3c4 and related NOD ABD strains is caused by a chromosome 1 region that includes a novel mutation in polycystic kidney and hepatic disease 1 (Pkhd1). We show that a long terminal repeat element inserted into intron 35 exposes an alternative polyadenylation site, resulting in a truncated Pkhd1 transcript...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29154966/determinants-of-fibrosis-progression-and-regression-in-nash
#19
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
#20
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
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