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Cholangiocyte hepatocyte

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https://www.readbyqxmd.com/read/28213465/epithelial-morphogenesis-during-liver-development
#1
Naoki Tanimizu, Toshihiro Mitaka
Tissue stem/progenitor cells supply multiple types of epithelial cells that eventually acquire specialized functions during organ development. In addition, three-dimensional (3D) tissue structures need to be established for organs to perform their physiological functions. The liver contains two types of epithelial cells, namely, hepatocytes and cholangiocytes, which are derived from hepatoblasts, fetal liver stem/progenitor cells (LPCs), in mid-gestation. Hepatocytes performing many metabolic reactions form cord-like structures, whereas cholangiocytes, biliary epithelial cells, form tubular structures called intrahepatic bile ducts...
February 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28135758/the-diversity-and-plasticity-of-adult-hepatic-progenitor-cells-and-their-niche
#2
REVIEW
Jiamei Chen, Long Chen, Mark A Zern, Neil D Theise, Ann Mae Diehl, Ping Liu, Yuyou Duan
The liver is a unique organ for homoeostasis with regenerative capacities. Hepatocytes possess a remarkable capacity to proliferate upon injury; however, in more severe scenarios liver regeneration is believed to arise from at least one, if not several facultative hepatic progenitor cell compartments. Newly identified pericentral stem/progenitor cells residing around the central vein is responsible for maintaining hepatocyte homoeostasis in the uninjured liver. In addition, hepatic progenitor cells have been reported to contribute to liver fibrosis and cancers...
January 30, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28120434/the-role-of-s1pr2-in-bile-acid-induced-cholangiocyte-proliferation-and-cholestasis-induced-liver-injury-in-mice
#3
Yongqing Wang, Hiroaki Aoki, Jing Yang, Kesong Peng, Runping Liu, Xiaojiaoyang Li, Xiaoyan Qiang, Lixin Sun, Emily C Gurley, Guanhua Lai, Luyong Zhang, Guang Liang, Masayuki Nagahashi, Kazuaki Takabe, William M Pandak, Phillip B Hylemon, Huiping Zhou
Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially for large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the AKT and ERK1/2 signaling pathways via the sphingosine 1-phosphate receptor 2 (S1PR2) in hepatocytes and cholangiocarcinoma cells. It also has been reported that taurocholate (TCA) promotes large cholangiocyte proliferation and protects cholangiocytes from bile duct ligation (BDL)-induced apoptosis. However, the role of S1PR2 in bile acid-mediated cholangiocyte proliferation and cholestatic liver injury has not been elucidated...
January 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28088462/activation-of-the-hypoxia-inducible-factor-1-alpha-subunit-pathway-in-steatotic-liver-contributes-to-formation-of-cholesterol-gallstones
#4
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
BACKGROUND AND AIMS: Hypoxia inducible factor 1 alpha subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD increases risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes, via a Cre adenoviral vector (iH-HIFKO mice), and mice without disruption of Hif1a (control mice)...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28055309/current-strategies-to-generate-mature-human-induced-pluripotent-stem-cells-derived-cholangiocytes-and-future-applications
#5
Eduardo Cervantes-Alvarez, Yang Wang, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Jiye Zhu, Kazuki Takeishi
Stem cell research has significantly evolved over the last few years, allowing the differentiation of pluripotent cells into almost any kind of lineage possible. Studies that focus on the liver have considerably taken a leap into this novel technology, and hepatocyte-like cells are being generated that are close to resembling actual hepatocytes both genotypically and phenotypically. The potential of this extends from disease models to bioengineering, and even also innovative therapies for end-stage liver disease...
January 2, 2017: Organogenesis
https://www.readbyqxmd.com/read/28029279/recellularization-via-the-bile-duct-supports-functional-allogenic-and-xenogenic-cell-growth-on-a-decellularized-rat-liver-scaffold
#6
Wessam Hassanein, Mehmet C Uluer, John Langford, Jhade D Woodall, Arielle Cimeno, Urmil Dhru, Avraham Werdesheim, Joshua Harrison, Carlos Rivera-Pratt, Stephen Klepfer, Ali Khalifeh, Bryan Buckingham, Philip S Brazio, Dawn Parsell, Charlie Klassen, Cinthia Drachenberg, Rolf N Barth, John C LaMattina
Recent years have seen a proliferation of methods leading to successful organ decellularization. In this experiment we examine the feasibility of a decellularized liver construct to support growth of functional multilineage cells. Bio-chamber systems were used to perfuse adult rat livers with 0.1% SDS for 24 hours yielding decellularized liver scaffolds. Initially, we recellularized liver scaffolds using a human tumor cell line (HepG2, introduced via the bile duct). Subsequent studies were performed using either human tumor cells co-cultured with human umbilical vein endothelial cells (HUVECs, introduced via the portal vein) or rat neonatal cell slurry (introduced via the bile duct)...
January 2, 2017: Organogenesis
https://www.readbyqxmd.com/read/28009756/regeneration-and-cell-recruitment-in-an-improved-heterotopic-auxiliary-partial-liver-transplantation-model-in-the-rat
#7
Yoshihiro Ono, Angelica Pérez-Gutiérrez, Mladen I Yovchev, Kentaro Matsubara, Shinichiro Yokota, Jorge Guzman-Lepe, Kan Handa, Alexandra Collin de l'Hortet, Angus W Thomson, David A Geller, Hiroshi Yagi, Michael Oertel, Alejandro Soto-Gutierrez
BACKGROUND: Auxiliary partial liver transplantation (APLT) in humans is a therapeutic modality used especially to treat liver failure in children or congenital metabolic disease. Animal models of APLT have helped to explore therapeutic options. Though many groups have suggested improvements, standardizing the surgical procedure has been challenging. Additionally, the question of whether graft livers are reconstituted by recipient-derived cells after transplantation has been controversial...
January 2017: Transplantation
https://www.readbyqxmd.com/read/27981602/prohibitin-1-suppresses-liver-cancers-tumorigenesis-in-mice-and-human-hepatocellular-and-cholangiocarcinoma-cells
#8
Wei Fan, Heping Yang, Ting Liu, Jiaohong Wang, Tony W H Li, Nirmala Mavila, Yuanyuan Tang, JinWon Yang, Hui Peng, Jian Tu, Alagappan Annamalai, Mazen Noureddin, Anuradha Krishnan, Gregory J Gores, M L Martínez-Chantar, José M Mato, Shelly C Lu
: Prohibitin 1 (PHB1) is best known as a mitochondrial chaperone and its role in cancer is conflicting. Mice lacking methionine adenosyltransferase α 1 (MATα1) have lower PHB1 expression and we reported c-MYC interacts directly with both proteins. Furthermore, c-MYC and MATα1 expert opposing effects on liver cancer growth, prompting us to examine the interplay between PHB1, MATα1 and c-MYC and PHB1's role in liver tumorigenesis. We found PHB1 is highly expressed in normal hepatocytes and bile duct epithelial cells and down-regulated in most human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA)...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27979827/protective-roles-of-hepatic-gaba-signaling-in-acute-liver-injury-of-rats
#9
Shuanglian Wang, Yun-Yan Xiang, Jianchun Zhu, Fan Yi, Jingxin Li, Chuanyong Liu, Wei-Yang Lu
Gamma-aminobutyric acid (GABA) is produced by various cells through the catalytic activity of glutamic acid decarboxylase (GAD). Activation of type-A GABA receptor (GABAAR) inhibits stem cell proliferation but protects differentiated cells from injures. The present study investigated hepatic GABA signaling system and the role of this system in liver physiology and pathophysiology. RT-PCR and immunoblot assays identified GAD and GABAAR subunits in rat livers and in HepG2 and Clone 9 hepatocytes. Patch-clamp recording detected GABA-induced currents in Clone 9 hepatocytes and depolarization in WITT cholangiocytes...
December 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27979774/gene-regulatory-networks-in-differentiation-and-direct-reprogramming-of-hepatic-cells
#10
REVIEW
Claude Gérard, Janne Tys, Frédéric P Lemaigre
Liver development proceeds by sequential steps during which gene regulatory networks (GRNs) determine differentiation and maturation of hepatic cells. Characterizing the architecture and dynamics of these networks is essential for understanding how cell fate decisions are made during development, and for recapitulating these processes during in vitro production of liver cells for toxicology studies, disease modelling and regenerative therapy. Here we review the GRNs that control key steps of liver development and lead to differentiation of hepatocytes and cholangiocytes in mammals...
December 12, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27916538/myofibroblasts-derived-from-hepatic-progenitor-cells-create-the-tumor-microenvironment
#11
Sayaka Sekiya, Shizuka Miura, Kanae Matsuda-Ito, Atsushi Suzuki
Hepatic progenitor cells (HPCs) appear in response to several types of chronic injury in the human and rodent liver that often develop into liver fibrosis, cirrhosis, and primary liver cancers. However, the contribution of HPCs to the pathogenesis and progression of such liver diseases remains controversial. HPCs are generally defined as cells that can differentiate into hepatocytes and cholangiocytes. In this study, however, we found that HPCs isolated from the chronically injured liver can also give rise to myofibroblasts as a third type of descendant...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#12
Ursula J Lemberger, Claudia Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27881141/analysis-of-epithelial-mesenchymal-transition-markers-in-the-histogenesis-of-hepatic-progenitor-cell-in-hbv-related-liver-diseases
#13
Wei Xu, Nong-Rong Wang, Hua-Feng Wang, Qiong Feng, Jun Deng, Zhi-Qiang Gong, Jian Sun, Xiao-Liang Lou, Xue-Feng Yu, Lv Zhou, Jin-Ping Hu, Xiao-Feng Huang, Xiao-Qing Qi, Yan-Juan Deng, Rui Gong, Yan Guo, Meng-Meng Wang, Jia-Cheng Xiao, Huan Deng
BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection...
November 24, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27826954/critical-and-diverse-in-vivo-roles-of-apoptosis-signal-regulating-kinase-1-in-animal-models-of-atherosclerosis-and-cholestatic-liver-injury
#14
REVIEW
Sohsuke Yamada, Hirotsugu Noguchi, Akihide Tanimoto
Apoptosis plays pivotal in vivo roles in not only vital processes, such as cell turnover and embryonic development, but also various inflammatory disorders. However, the role of apoptosis by vascular and hepatic cells in the respective progression of atherosclerosis and liver injury remains controversial. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase family member that is activated through distinct mechanisms in response to various cytotoxic stressors. ASK1, ubiquitously expressed, is situated in an important upstream position for many signal transduction pathways, which subsequently induce inflammation and/or apoptosis...
November 9, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27826058/the-progenitor-cell-dilemma-cellular-and-functional-heterogeneity-in-assistance-or-escalation-of-liver-injury
#15
REVIEW
Veronika Lukacs-Kornek, Frank Lammert
Liver progenitor cells (LPCs) are quiescent cells that are activated during liver injury and thought to give rise to hepatocytes and cholangiocytes in order to support liver regeneration and tissue restitution. While hepatocytes are capable of self-renewal, during most chronic injuries the proliferative capacity of hepatocytes is inhibited thus LPCs provide main source for regeneration. Despite extensive lineage tracing studies, their role and involvement in these processes are often controversial. Additionally, increasing evidence suggest that the LPC compartment consists of heterogeneous cell populations that are actively involved in cellular interactions with myeloid and lymphoid cells during regeneration...
November 5, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27789682/disrupted-murine-gut-to-human-liver-signaling-alters-bile-acid-homeostasis-in-humanized-mouse-liver-models
#16
Edwin C Y Chow, Holly P Quach, Yueping Zhang, Jason Z Y Wang, David C Evans, Albert P Li, Jose Silva, Rommel G Tirona, Yurong Lai, K Sandy Pang
The humanized liver mouse model is being exploited increasingly for human drug metabolism studies. However, its model stability, intercommunication between human hepatocytes and mouse nonparenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expressions have not been investigated. We examined these issues in FRGN [fumarylacetoacetate hydrolase (Fah-/-), recombination activating gene 2 (Rag2-/-), and interleukin 2 receptor subunit gamma (IL-2rg -/-) triple knockout] on nonobese diabetic (NOD) background] and chimeric mice: mFRGN and hFRGN (repopulated with mouse or human hepatocytes, respectively)...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27777588/a-transcriptomic-signature-of-mouse-liver-progenitor-cells
#17
Adam M Passman, Jasmine Low, Roslyn London, Janina E E Tirnitz-Parker, Atsushi Miyajima, Minoru Tanaka, Helene Strick-Marchand, Gretchen J Darlington, Megan Finch-Edmondson, Scott Ochsner, Cornelia Zhu, James Whelan, Bernard A Callus, George C T Yeoh
Liver progenitor cells (LPCs) can proliferate extensively, are able to differentiate into hepatocytes and cholangiocytes, and contribute to liver regeneration. The presence of LPCs, however, often accompanies liver disease and hepatocellular carcinoma (HCC), indicating that they may be a cancer stem cell. Understanding LPC biology and establishing a sensitive, rapid, and reliable method to detect their presence in the liver will assist diagnosis and facilitate monitoring of treatment outcomes in patients with liver pathologies...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27769530/inactivation-of-p120-catenin-in-mice-disturbs-intrahepatic-bile-duct-development-and-aggravates-liver-carcinogenesis
#18
Jolanda van Hengel, Celine Van den Broeke, Tim Pieters, Louis Libbrecht, Ilse Hofmann, Frans van Roy
p120 catenin (p120ctn) is required for the stability of classic cadherins at the cell surface and is thought to play a central role in modulating cell-cell adhesion. Cytoplasmic p120ctn promotes cell motility, and probably other activities, by modulating the activities of RhoA, Rac and Cdc42. E-cadherin is expressed in periportal but not in perivenous hepatocytes. In contrast, all hepatocytes of normal mouse liver express N-cadherin. Cholangiocytes express exclusively E-cadherin. Mice with p120ctn ablation in hepatocytes and cholangiocytes (p120LiKO mice) were generated by Cre-loxP technology...
December 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27762150/epigenetic-regulation-of-hepatic-stellate-cell-activation-and-liver-fibrosis
#19
Adil El Taghdouini, Leo A van Grunsven
Chronic liver injury to hepatocytes or cholangiocytes, when left unmanaged, leads to the development of liver fibrosis, a condition characterized by the excessive intrahepatic deposition of extracellular matrix proteins. Activated hepatic stellate cells constitute the predominant source of extracellular matrix in fibrotic livers and their transition from a quiescent state during fibrogenesis is associated with important alterations in their transcriptional and epigenetic landscape. Areas covered: We briefly describe the processes involved in hepatic stellate cell activation and discuss our current understanding of alterations in the epigenetic landscape, i...
December 2016: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27748507/p62-promotes-amino-acid-sensitivity-of-mtor-pathway-and-hepatic-differentiation-in-adult-liver-stem-progenitor-cells
#20
Masakazu Sugiyama, Tomoharu Yoshizumi, Yoshihiro Yoshida, Yuki Bekki, Yoshihiro Matsumoto, Shohei Yoshiya, Takeo Toshima, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Shinji Okano, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara
Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62 and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically-induced liver injury...
October 17, 2016: Journal of Cellular Physiology
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