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Hepatocyte polarity

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https://www.readbyqxmd.com/read/29404462/intermittent-hypoxia-is-a-proinflammatory-stimulus-resulting-in-il-6-expression-and-m1-macrophage-polarization
#1
Esperance Schaefer, Winona Wu, Christina Mark, Andrew Yang, Erik DiGiacomo, Charles Carlton-Smith, Shadi Salloum, Cynthia Brisac, Wenyu Lin, Kathleen E Corey, Raymond T Chung
The biological factors that promote inflammation or nonalcoholic steatohepatitis (NASH) in the setting of nonalcoholic fatty liver disease remain incompletely understood. Clinical studies have demonstrated an association between obstructive sleep apnea (OSA) and both inflammation and fibrosis in NASH, but the mechanism has not been identified. In this study, we use in vitro modeling to examine the impact of intermittent hypoxia on the liver. Hepatocyte, stellate cell, and macrophage cell lines were exposed to intermittent or sustained hypoxia...
June 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29404441/the-role-of-human-cytochrome-p450-2e1-in-liver-inflammation-and-fibrosis
#2
Jun Xu, Hsiao-Yen Ma, Shuang Liang, Mengxi Sun, Gabriel Karin, Yukinori Koyama, Ronglin Hu, Oswald Quehenberger, Nicholas O Davidson, Edward A Dennis, Tatiana Kisseleva, David A Brenner
Cytochrome P450 2E1 ( CYP2E1 ) plays an important role in alcohol and toxin metabolism by catalyzing the conversion of substrates into more polar metabolites and producing reactive oxygen species. Reactive oxygen species-induced oxidative stress promotes hepatocyte injury and death, which in turn induces inflammation, activation of hepatic stellate cells, and liver fibrosis. Here, we analyzed mice expressing only the human CYP2E1 gene (hCYP2E1) to determine differences in hCYP2E1 versus endogenous mouse Cyp2e1 function with different liver injuries...
December 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29366910/tgf%C3%AE-1-mediated-suppression-of-cytochrome-p450-cyp-induction-responses-in-rat-hepatocyte-fibroblast-co-cultures
#3
Yu Yu, A Ananthanarayanan, Nisha Hari Singh, Xin Hong, Rashidah Binte Sakban, Nikhil Mittal, Luo Xiaobei, Jeffrey Robens, Lei Xia, Michael McMillian, Hanry Yu
Co-culture of hepatocyte and fibroblasts has shown distinct advantages in enhancing certain liver specific functions and maintaining hepatic polarity. However, the utility of hepatocyte co-culture models for studies, such as drug-drug interaction studies, has not been completely elucidated. In this study the induction of Cyp1a2, Cyp2b1/2, and Cyp3a2, the three major cytochrome P450 (CYP) isoforms in the rat liver, was evaluated in randomly mixed co-cultures and micropatterned co-cultures. We found that in both co-culture configurations, the drug-induced Cyp1a2, Cyp2b1/2, Cyp3a2 mRNA and activity were suppressed relative to those in monocultured hepatocytes...
January 20, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29356040/basolateral-cd147-induces-hepatocyte-polarity-loss-by-e-cadherin-ubiquitination-and-degradation-in-hepatocellular-carcinoma-progress
#4
Meng Lu, Jiao Wu, Zhi-Wei Hao, Yu-Kui Shang, Jing Xu, Gang Nan, Xia Li, Zhi-Nan Chen, Huijie Bian
Hepatocytes are epithelial cells with highly specialized polarity. The disorder and loss of hepatocyte polarity lead to the weakness of cell adhesion and connection, the induction of epithelial-mesenchymal transition and eventually the occurrence of hepatocellular carcinoma (HCC). CD147, a tumor-related glycoprotein, promotes epithelial-mesenchymal transition and the invasion of HCC. However, the function of CD147 in hepatocyte depolarization is unknown. Here we identified that CD147 was basolaterally polarized in hepatocyte membrane of liver tissues and HepG2 cells...
January 21, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29312604/serum-amyloid-a-induces-m2b-like-macrophage-polarization-during-liver-inflammation
#5
Yibin Wang, Haijun Huang, Renhua Sun, Bingyu Chen, Fang Han, Qian Li, Yin Ni, Xi Li, Jingquan Liu, Xiaozhou Mou, Yuexing Tu
Hepatitis causes hepatic cell injury, regeneration and different levels of fibrogenesis, and severe liver fibrogenesis progresses into cirrhosis with liver dysfunction. Serum amyloid A (SAA) is an acute phase protein that is predominantly secreted by hepatocytes during early injury or infection. Nevertheless, the relationship of SAA and development of cirrhosis as well as the underlying molecular mechanisms is largely unknown. Here, we found that macrophages are the major SAA-binding cells in the injured liver...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286119/perioperative-oral-supplementation-with-fish-oil-promotes-liver-regeneration-following-partial-hepatectomy-in-mice-via-ampk-activation
#6
Hui Yao, Xiao Fu, Xuejian Zi, Wenjun Jia, Yudong Qiu
The present study aimed to observe the effects of perioperative oral supplementation with fish oil (FO) on liver regeneration in mice and examine the potential mechanism. A total of 120 male ICR mice were randomly divided into 5 groups: Sham, Control, fish oil (FO), Compound C [the AMP‑activated protein kinase (AMPK) inhibitor dorsomorphin], and Compound C + FO. Changes in liver function, alterations in hepatocyte proliferation and in the expression of polarization markers, and activation of AMPK signaling were examined following partial hepatectomy (PH)...
December 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29259373/mesenchymal-stem-cells-rescue-acute-hepatic-failure-by-polarizing-m2-macrophages
#7
Yan-Wei Li, Chong Zhang, Qiu-Ju Sheng, Han Bai, Yang Ding, Xiao-Guang Dou
AIM: To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells (MSCs) in acute hepatic failure (AHF). METHODS: MSCs were transfused into rats with AHF induced by D-galactosamine (DGalN). The therapeutic effects of MSCs were evaluated based on survival rate and hepatocyte proliferation and apoptosis. Hepatocyte regeneration capacity was evaluated by the expression of the hepatic progenitor surface marker epithelial cell adhesion molecule (EpCAM)...
December 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29251434/macrophage-p38-kinase-inhibition-for-liver-regeneration
#8
Klaus Schulze-Osthoff, Heike Bantel
In this issue, Ying et al. show that p38α kinase (MAPK14) controls macrophage polarization following acute liver injury. Myeloid cell-specific depletion of p38α promotes polarization to anti-inflammatory M2 macrophages and prevents pro-inflammatory cytokine secretion that ameliorate acute liver injury and promotes hepatocyte proliferation. Therapeutic targeting of macrophage p38α is an attractive strategy not only to suppress inflammation, but also to support liver regeneration.
December 2017: FEBS Journal
https://www.readbyqxmd.com/read/29238913/phthalazinone-pyrazole-enhances-the-hepatic-functions-of-human-embryonic-stem-cell-derived-hepatocyte-like-cells-via-suppression-of-the-epithelial-mesenchymal-transition
#9
Young-Jun Choi, Hyemin Kim, Ji-Woo Kim, Chang-Woo Song, Dae-Sung Kim, Seokjoo Yoon, Han-Jin Park
During liver development, nonpolarized hepatic progenitor cells differentiate into mature hepatocytes with distinct polarity. This polarity is essential for maintaining the intrinsic properties of hepatocytes. The balance between the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) plays a decisive role in differentiation of polarized hepatocytes. In this study, we found that phthalazinone pyrazole (PP), a selective inhibitor of Aurora-A kinase (Aurora-A), suppressed the EMT during the differentiation of hepatocyte-like cells (HLCs) from human embryonic stem cells...
December 13, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29237808/human-fetal-liver-cultures-support-multiple-cell-lineages-that-can-engraft-immunodeficient-mice
#10
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/29218530/tracking-glut2-translocation-by-live-cell-imaging
#11
Sabina Tsytkin-Kirschenzweig, Merav Cohen, Yaakov Nahmias
The facilitative glucose transporter (GLUT) family plays a key role in metabolic homeostasis, controlling the absorption rates and rapid response to changing carbohydrate levels. The facilitative GLUT2 transporter is uniquely expressed in metabolic epithelial cells of the intestine, pancreas, liver, and kidney. GLUT2 dysfunction is associated with several pathologies, including Fanconi-Bickel syndrome, a glycogen storage disease, characterized by growth retardation and renal dysfunction. Interestingly, GLUT2 activity is modulated by its cellular localization...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29218485/apical-membrane-alterations-in-non-intestinal-organs-in-microvillus-inclusion-disease
#12
Cameron Schlegel, Victoria G Weis, Byron C Knowles, Lynne A Lapierre, Martin G Martin, Paul Dickman, James R Goldenring, Mitchell D Shub
OBJECTIVES: Microvillus inclusion disease (MVID) is a severe form of neonatal diarrhea, caused mainly by mutations in MYO5B. Inactivating mutations in MYO5B causes depolarization of enterocytes in the small intestine, which gives rise to chronic, unremitting secretory diarrhea. While the pathology of the small intestine in MVID patients is well described, little is known about extraintestinal effects of MYO5B mutation. METHODS: We examined stomach, liver, pancreas, colon, and kidney in Navajo MVID patients, who share a single homozygous MYO5B-P660L (1979C>T p...
December 7, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29166570/splenectomy-after-partial-hepatectomy-accelerates-liver-regeneration-in-mice-by-promoting-tight-junction-formation-via-polarity-protein-par-3-apkc
#13
Guoxing Liu, Chengzhi Xie, Yu Fang, Ke Qian, Qiang Liu, Gao Liu, Zhenyu Cao, Huihui Du, Jie Fu, Xundi Xu
AIMS: Several experimental studies have demonstrated that removal of the spleen accelerates liver regeneration after partial hepatectomy. While the mechanism of splenectomy promotes liver regeneration by the improvement of the formation of tight junction and the establishment of hepatocyte polarity is still unknown. MAIN METHODS: We analyzed the cytokines, genes and proteins expression between 70% partial hepatectomy mice (PHx) and simultaneous 70% partial hepatectomy and splenectomy mice (PHs) at predetermined timed points...
November 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/29113177/potential-role-of-indoleamine-2-3-dioxygenase-in-primary-biliary-cirrhosis
#14
Kashif Asghar, John Brain, Jeremy M Palmer, Stephen Douglass, Fatmah M A Naemi, Graeme O'Boyle, John Kirby, Simi Ali
Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29095348/di-2-ethylhexyl-phthalate-and-its-role-in-developing-cholestasis-an-in-vitro-study-on-different-liver-cell-types
#15
Haristi Gaitantzi, Priska Hakenberg, Jannick Theobald, Hagen Heinlein, Chen Cai, Steffan Loff, Stefan Wölfl, Matthias P Ebert, Katja Breitkopf-Heinlein, Ulrike Subotic
OBJECTIVES: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in many polyvinylchloride medical devices and is washed out easily. Thereby critically ill infants can become exposed to DEHP concentrations significantly exceeding the recommended threshold. We suspect DEHP to play an important role in the development of intestinal failure associated liver disease. The aim of this study was therefore, to determine the direct influence of DEHP on different liver cell types. METHODS: HepG2, human upcyte hepatocytes, primary murine hepatocytes, LX-2, human upcyte hepatic stellate cells and liver organoids were cultured with DEHP (0...
October 31, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29052963/deficiency-of-p38%C3%AE-in-macrophage-ameliorates-d-galactosamine-tnf-%C3%AE-induced-acute-liver-injury-in-mice
#16
Jiao Liu, Shengjie Zhang, Hongchao Cao, Hui Wang, Chao Sun, Shengnan Liu, Shuxian Yu, Yan Li, Wei Liu, Hui Wang, Jingjing Jiang, Hao Ying
Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells and promoting hepatocyte proliferation. Understanding the role of macrophage in the pathogenesis of liver injury will help pave the way to future therapeutics. Here we investigated whether macrophage p38α plays a regulatory role in the tissue repair following a GalN/TNF-α-induced acute liver injury. We found that macrophage p38α deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF-α treatment...
October 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29052367/decellularized-caprine-liver-extracellular-matrix-as-a-2d-substrate-coating-and-3d-hydrogel-platform-for-vascularized-liver-tissue-engineering
#17
Tarun Agarwal, Rajan Narayan, Somnath Maji, Sudip Kumar Ghosh, Tapas Kumar Maiti
Development of a vascularized liver tissue construct is a need of an hour to circumvent the current demand of liver transplantation in healthcare sector. An appropriate matrix must support liver cell viability, functionality, and development of microvasculature. With this perspective, here, we report the use of decellularized Caprine liver ECM (CLECM) derived hydrogel for tissue engineering applications. First, CLECM was used as a substrate coating material for 2D hepatocyte culture. HepG2 cells cultured on CLECM coated surface showed higher albumin, urea, glycogen and GAGs synthesis in comparison to collagen coated surface (taken as control for the study)...
October 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29050073/-clinicopathologic-features-of-three-cases-of-erythropoietic-protoporphyria-with-liver-involvement
#18
J Shi, X Q Li, Z H Lu
Objective: To investigate the clinicopathologic features of the erythropoietic protoporphyria (EPP) with liver involvement. Methods: The clinical findings and hepatic biopsy of 3 cases of EPP diagnosed between July, 2011 to August, 2014 with liver involvement were reviewed, with relevant literature review. Results: All patients presented with persistent and refractory abdominal pain, with obvious jaundice and deranged liver function. Imaging showed homogeneous hepatomegaly in all patients. Histologically, the hepatocytes were edematous, and contained numerous cytoplasmic globular brown pigments and bile pigments, which were also found in Kupffer cells, in the bile canaliculi and in some of dilated sinusoid...
October 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28986171/early-indications-of-anit-induced-cholestatic-liver-injury-alteration-of-hepatocyte-polarization-and-bile-acid-homeostasis
#19
Tingting Yang, Huifang Mei, Dengqiu Xu, Wang Zhou, Xiaoyu Zhu, Lixin Sun, Xin Huang, Xue Wang, Ting Shu, Jia Liu, Jiaxin Ding, H M Hassan, Luyong Zhang, Zhenzhou Jiang
Hepatocyte polarization is essential for biliary secretion, and loss of polarity causes bile secretory failure and hepatotoxicity. Here, we showed that alpha-naphthyl isothiocyanate (ANIT)-induced liver injury was accompanied by the dynamic interruption of bile acid homeostasis in rat plasma, liver and bile, which was characterized by the redistribution of bile acids in plasma and bile and a small range of fluctuations in the liver. Molecular mechanism studies indicated that these factors are dynamically mediated by the disruption of bile acid transporters and hepatic tight junctions...
October 3, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28940700/therapeutic-inhibition-of-inflammatory-monocyte-recruitment-reduces-steatohepatitis-and-liver-fibrosis
#20
Oliver Krenkel, Tobias Puengel, Olivier Govaere, Ali T Abdallah, Jana C Mossanen, Marlene Kohlhepp, Anke Liepelt, Eric Lefebvre, Tom Luedde, Claus Hellerbrand, Ralf Weiskirchen, Thomas Longerich, Ivan G Costa, Quentin M Anstee, Christian Trautwein, Frank Tacke
Macrophages are key regulators of liver fibrosis progression and regression in nonalcoholic steatohepatitis (NASH). Liver macrophages comprise resident phagocytes, Kupffer cells, and monocyte-derived cells, which are recruited via the chemokine receptor CCR2. We aimed at elucidating the therapeutic effects of inhibiting monocyte infiltration in NASH models by using cenicriviroc (CVC), an oral dual chemokine receptor CCR2/CCR5 antagonist that is under clinical evaluation. Human liver tissue from NASH patients were analyzed for CCR2+ macrophages and administration of CVC was tested in mouse models of steatohepatitis, liver fibrosis progression and fibrosis regression...
September 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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