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Cholangiocyte hepatocyte

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https://www.readbyqxmd.com/read/29154966/determinants-of-fibrosis-progression-and-regression-in-nash
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28903311/development-of-hepatoma-derived-bidirectional-oval-like-cells-as-a-model-to-study-host-interactions-with-hepatitis-c-virus-during-differentiation
#13
Masahiko Ito, Suofeng Sun, Takasuke Fukuhara, Ryosuke Suzuki, Miho Tamai, Toyohiko Yamauchi, Kenji Nakashima, Yoh-Ichi Tagawa, Shigetoshi Okazaki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
Directed differentiation of human stem cells including induced pluripotent stem cells into hepatic cells potentially leads to acquired susceptibility to hepatitis C virus (HCV) infection. However, cellular determinants that change their expression during cell reprogramming or hepatic differentiation and are pivotal for supporting the HCV life cycle remain unclear. In this study, by introducing a set of reprogramming factors, we established HuH-7-derived oval-like cell lines, Hdo-17 and -23, which possess features of bipotential liver precursors...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878125/human-hepatic-organoids-for-the-analysis-of-human-genetic-diseases
#14
Yuan Guan, Dan Xu, Phillip M Garfin, Ursula Ehmer, Melissa Hurwitz, Greg Enns, Sara Michie, Manhong Wu, Ming Zheng, Toshihiko Nishimura, Julien Sage, Gary Peltz
We developed an in vitro model system where induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional human hepatic organoids (HOs) through stages that resemble human liver during its embryonic development. The HOs consist of hepatocytes, and cholangiocytes, which are organized into epithelia that surround the lumina of bile duct-like structures. The organoids provide a potentially new model for liver regenerative processes, and were used to characterize the effect of different JAG1 mutations that cause: (a) Alagille syndrome (ALGS), a genetic disorder where NOTCH signaling pathway mutations impair bile duct formation, which has substantial variability in its associated clinical features; and (b) Tetralogy of Fallot (TOF), which is the most common form of a complex congenital heart disease, and is associated with several different heritable disorders...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28853804/-benign-focal-liver-lesions-a-clinical-radiological-and-pathological-review
#15
Karim Abdelrahman, Sabine Schmidt, Amedeo Sciarra, Christine Sempoux
Benign focal liver lesions are a heterogeneous group of tumors of different cellular origin. They might develop from mesenchymal cells, hepatocytes or cholangiocytes. They are more often detected due to the increasing number of imaging investigations and the excellent performance of the new ultrasound machines. The imaging findings have to be interpreted while bearing the patient's clinical context in mind. The aim of this review is to discuss the three most frequent benign focal hepatic lesions : hemangioma, focal nodular hyperplasia and hepatocellular adenoma...
August 30, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28834615/self-assembled-liver-organoids-recapitulate-hepato-biliary-organogenesis-in-vitro
#16
Dipen Vyas, Pedro M Baptista, Matthew Brovold, Emma Moran, Matthew Brovold, Brandon Gaston, Chris Booth, Michael Samuel, Anthony Atala, Shay Soker
Several 3D cell culture systems are currently available to create liver organoids. In general, these systems display better physiologic and metabolic aspects of intact liver tissue, compared with 2D culture systems. However, none of these reliably mimic human liver development, including parallel formation of hepatocyte and cholangiocyte anatomical structures. Here, we show that human fetal liver progenitor cells self-assemble inside acellular liver extracellular matrix (ECM) scaffolds to form 3D liver organoids that recapitulated several aspects of hepato-biliary organogenesis and resulted in concomitant formation of progressively more differentiated hepatocytes and bile duct structures...
August 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28833283/mir-337-3p-controls-hepatobiliary-gene-expression-and-transcriptional-dynamics-during-hepatic-cell-differentiation
#17
Céline Demarez, Claude Gérard, Sabine Cordi, Alexis Poncy, Younes Achouri, Nicolas Dauguet, David A Rosa, Patrick T Gunning, Isabelle Manfroid, Frédéric P Lemaigre
Transcriptional networks control the differentiation of the hepatocyte and cholangiocyte lineages from embryonic liver progenitor cells, and their subsequent maturation to the adult phenotype. However, how accurate levels of hepatocyte and cholangiocyte gene expression are determined during differentiation remains poorly understood. Here we identify miR-337-3p as a novel regulator of liver development. MiR-337-3p stimulates expression of cholangiocyte genes and represses hepatocyte genes in undifferentiated progenitor cells in vitro and in embryonic mouse livers...
August 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28794318/dysregulated-expression-of-mitf-in-subsets-of-hepatocellular-carcinoma-and-cholangiocarcinoma
#18
Nattakarn Nooron, Koji Ohba, Kazuhisa Takeda, Shigeki Shibahara, Anchalee Chiabchalard
Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array...
August 2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28777941/cholangiocytes-no-longer-cinderellas-to-the-hepatic-regenerative-response
#19
Malcolm R Alison
Biliary ductal cells proliferate from the portal areas of chronically damaged livers, but their significance to regeneration has been controversial. A recent article in Nature by Raven et al. (2017) now shows that blocking hepatocyte replication is essential for the hepatic differentiation of ductular cells after liver damage.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28777871/the-functional-characteristics-ccni-modulation-of-myeloid-derived-suppressor-cells-in-liver-inflammation
#20
Haiyan Zhang, Min Lian, Jun Zhang, Zhaolian Bian, Ruqi Tang, Qi Miao, Yanshen Peng, Jingyuan Fang, Zhengrui You, Pietro Invernizzi, Qixia Wang, M Eric Gershwin, Xiong Ma
There is increasing awareness of the immunologic roles of liver mononuclear populations including myeloid-derived suppressor cells (MDSCs). We took advantage of a large well defined cohort of 148 patients with liver inflammation and 45 health controls to focus on the qualitative and quantitative characteristics of MDSCs. We investigated the frequency, phenotype and functional capacities of MDSCs using peripheral blood MDSCs in a cohort of 55 patients with PBC, 40 with AIH, 39 with CHB, 14 with NAFLD and 45 healthy controls, and thereafter a liver targeted determination in 27 PBC, 27 AIH, 20 CHB, 14 NAFLD and 6 controls...
August 4, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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