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Cholangiocyte hepatocyte

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https://www.readbyqxmd.com/read/29774067/estrogen-receptors-orchestrate-cell-growth-and-differentiation-to-facilitate-liver-regeneration
#1
Ta-Lun Kao, Yu-Ping Kuan, Wei-Chung Cheng, Wei-Chun Chang, Long-Bin Jeng, Shuyuan Yeh, Wen-Lung Ma
Background and Aims: Improving liver regeneration (LR) capacity and thereby liver function reserve is a critical bridging strategy for managing liver failure patients. Since estrogen signaling may participate in LR, our aim was to characterize the roles of ERα and ERβ in LR. Methods: LR capacity and estradiol levels following 2/3rd partial hepatectomy (PHx) were compared in ERα-KO or ERβ-KO vs. wildtype mice. The ERα- or ERβ-related transcriptome and interactome were analyzed from regenerating livers, and then bioinformatics was used for pathway discovery and analysis of interactome-transcriptome relationships...
2018: Theranostics
https://www.readbyqxmd.com/read/29720662/de-novo-formation-of-the-biliary-system-by-tgf%C3%AE-mediated-hepatocyte-transdifferentiation
#2
Johanna R Schaub, Kari A Huppert, Simone N T Kurial, Bernadette Y Hsu, Ashley E Cast, Bryan Donnelly, Rebekah A Karns, Feng Chen, Milad Rezvani, Hubert Y Luu, Aras N Mattis, Anne-Laure Rougemont, Philip Rosenthal, Stacey S Huppert, Holger Willenbring
Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche 1 . Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development-the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS) 2 ...
May 2, 2018: Nature
https://www.readbyqxmd.com/read/29673755/understanding-liver-regeneration-from-mechanisms-to-regenerative-medicine
#3
REVIEW
Hélène Gilgenkrantz, Alexandra Collin de l'Hortet
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities...
April 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29665133/isolation-of-a-unique-hepatic-stellate-cell-population-expressing-integrin-%C3%AE-8-from-embryonic-mouse-livers
#4
Tomohiro Ogawa, Yuchang Li, Ingrid Lua, Andrea Hartner, Kinji Asahina
BACKGROUND: Hepatic stellate cells (HSCs) play an important role in liver fibrogenesis. However, little is known about their phenotype and role in liver development. The aim of this study is to identify specific markers for embryonic HSCs. RESULTS: Using antibodies against ALCAM and PDPN, we separated mesothelial cells (MCs) and HSCs from developing livers and identified integrin α8 (ITGA8) as a marker for embryonic desmin+ HSCs that are preferentially localized near the developing liver surface and α-smooth muscle actin+ perivascular mesenchymal cells around the vein...
April 17, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29627454/expression-patterns-of-yes-associated-protein-1-in-the-developing-mouse-liver
#5
Wei Wei, Jeremy Lotto, Pamela A Hoodless
The Hippo signalling pathway regulates many cellular processes, but has been specifically associated with control organ size and tumor growth. Yes-associated protein 1 (YAP1) is a transcriptional cofactor, in the Hippo pathway, that regulates gene expression when localized in the nucleus. Elevated expression of YAP1 in adult mouse liver leads to hepatomegaly and can cause hepatocellular carcinoma; while the loss of function studies reveal its importance in regulating cholangiocyte development. Here, we report the expression of YAP1 in mouse embryonic and postnatal hepatic cells, using AFP-GFP transgenic mice to identify the hepatocyte lineage...
April 5, 2018: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29545603/notch2-controls-hepatocyte-derived-cholangiocarcinoma-formation-in-mice
#6
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
https://www.readbyqxmd.com/read/29545201/bromodomain-and-extraterminal-bet-proteins-regulate-hepatocyte-proliferation-in-hepatocyte-driven-liver-regeneration
#7
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 such as 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
https://www.readbyqxmd.com/read/29544731/autocrine-transforming-growth-factor-%C3%AE-activin-a-smad-signaling-induces-hepatic-progenitor-cells-undergoing-partial-epithelial-mesenchymal-transition-states
#8
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
https://www.readbyqxmd.com/read/29542689/corrigendum-cholangiocytes-act-as-facultative-liver-stem-cells-during-impaired-hepatocyte-regeneration
#9
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
https://www.readbyqxmd.com/read/29527264/multipotent-stromal-cells-stimulate-liver-regeneration-by-influencing-the-macrophage-polarization-in-rat
#10
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
https://www.readbyqxmd.com/read/29526886/wntless-is-highly-expressed-in-advanced-stage-intrahepatic-cholangiocarcinoma
#11
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
https://www.readbyqxmd.com/read/29523787/paracrine-cellular-senescence-exacerbates-biliary-injury-and-impairs-regeneration
#12
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
https://www.readbyqxmd.com/read/29509572/porcine-isolated-liver-perfusion-for-the-study-of-ischemia-reperfusion-injury-a-systematic-review
#13
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
https://www.readbyqxmd.com/read/29464551/immunohistochemical-assessment-of-the-expression-of-biliary-transportation-proteins-mrp2-and-mrp3-in-hepatocellular-carcinoma-and-in-cholangiocarcinoma
#14
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
https://www.readbyqxmd.com/read/29434290/induction-of-differentiation-of-intrahepatic-cholangiocarcinoma-cells-to-functional-hepatocytes-using-an-organoid-culture-system
#15
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
https://www.readbyqxmd.com/read/29429758/the-immunobiology-of-mucosal-associated-invariant-t-cell-mait-function-in-primary-biliary-cholangitis-regulation-by-cholic-acid-induced-interleukin-7
#16
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
https://www.readbyqxmd.com/read/29425397/cholangiocyte-derived-exosomal-long-noncoding-rna-h19-promotes-cholestatic-liver-injury-in-mouse-and-human
#17
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
https://www.readbyqxmd.com/read/29402311/hepatic-stem-cells-with-self-renewal-and-liver-repopulation-potential-are-harbored-in-cdcp1-positive-subpopulations-of-human-fetal-liver-cells
#18
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
https://www.readbyqxmd.com/read/29388792/transcription-factor-gata6-a-novel-marker-and-putative-inducer-of-ductal-metaplasia-in-biliary-atresia
#19
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
https://www.readbyqxmd.com/read/29360137/chcc-cca-consensus-terminology-for-primary-liver-carcinomas-with-both-hepatocytic-and-cholangiocytic-differentation
#20
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
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