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Hepatocyte polarity

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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
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28926118/chop-induced-loss-of-intestinal-epithelial-stemness-contributes-to-bile-duct-ligation-induced-cholestatic-liver-injury
#6
Runping Liu, Xiaojiaoyang Li, Zhiming Huang, Derrick Zhao, Bhagyalaxmi Sukka Ganesh, Guanhua Lai, William M Pandak, Phillip B Hylemon, Jasmohan S Bajaj, Arun J Sanyal, Huiping Zhou
Impaired intestinal barrier function promotes the progression of various liver diseases including cholestatic liver disease. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut-liver axis. It has been reported that bile duct ligation (BDL)-induced liver fibrosis is significantly reduced in C/EBP homologous protein knock out (CHOP(-/-) ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic ER stress responses after 1 day, which return to normal after 3 days...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28874845/m2-like-macrophages-in-the-fibrotic-liver-protect-mice-against-lethal-insults-through-conferring-apoptosis-resistance-to-hepatocytes
#7
Li Bai, Xin Liu, Qingfen Zheng, Ming Kong, Xiaohui Zhang, Richard Hu, Jinli Lou, Feng Ren, Yu Chen, Sujun Zheng, Shuang Liu, Yuan-Ping Han, Zhongping Duan, Stephen J Pandol
Acute injury in the setting of liver fibrosis is an interesting and still unsettled issue. Most recently, several prominent studies have indicated the favourable effects of liver fibrosis against acute insults. Nevertheless, the underlying mechanisms governing this hepatoprotection remain obscure. In the present study, we hypothesized that macrophages and their M1/M2 activation critically involve in the hepatoprotection conferred by liver fibrosis. Our findings demonstrated that liver fibrosis manifested a beneficial role for host survival and apoptosis resistance...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28862540/characterizing-cytotoxic-and-estrogenic-activity-of-arctic-char-tissue-extracts-in-primary-arctic-char-hepatocytes
#8
Karina Petersen, Maria T Hultman, Jenny Bytingsvik, Mikael Harju, Anita Evenset, Knut Erik Tollefsen
Contaminants from various anthropogenic activities are detected in the Arctic due to long-range atmospheric transport, ocean currents, and living organisms such as migrating fish or seabirds. Although levels of persistent organic pollutants (POPs) in Arctic fish are generally low, local hot spots of contamination were found in freshwater systems such as Lake Ellasjøen at Bjørnøya (Bear Island, Norway). Higher concentrations of organic halogenated compounds (OHC), and higher levels of cytochrome P450 and DNA-double strand breaks were reported in Arctic char (Salvelinus alpinus) from this lake compared to fish from other lakes on Bjørnøya...
2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#9
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28800633/feeding-fasting-dependent-recruitment-of-membrane-microdomain-proteins-to-lipid-droplets-purified-from-the-liver
#10
Kritika Sadh, Priyanka Rai, Roop Mallik
Lipid droplets (LDs) are cellular stores of neutral fat that facilitate lipid and protein trafficking in response to metabolic cues. Unlike other vesicles, the phospholipid membrane on the LD is a monolayer. Interestingly, this monolayer membrane has free cholesterol, and may therefore contain lipid microdomains that serve as a platform for assembling proteins involved in signal transduction, cell polarity, pathogen entry etc. In support of this, cell culture studies have detected microdomain-associated "raftophilic" proteins on LDs...
2017: PloS One
https://www.readbyqxmd.com/read/28749426/a-novel-perspective-on-the-apom-s1p-axis-highlighting-the-metabolism-of-apom-and-its-role-in-liver-fibrosis-and-neuroinflammation
#11
REVIEW
Stefan Hajny, Christina Christoffersen
Hepatocytes, renal proximal tubule cells as well as the highly specialized endothelium of the blood brain barrier (BBB) express and secrete apolipoprotein M (apoM). ApoM is a typical lipocalin containing a hydrophobic binding pocket predominantly carrying Sphingosine-1-Phosphate (S1P). The small signaling molecule S1P is associated with several physiological as well as pathological pathways whereas the role of apoM is less explored. Hepatic apoM acts as a chaperone to transport S1P through the circulation and kidney derived apoM seems to play a role in S1P recovery to prevent urinal loss...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28711771/toxicity-of-organic-compounds-from-unresolved-complex-mixtures-ucms-to-primary-fish-hepatocytes
#12
Karina Petersen, Maria T Hultman, Steven J Rowland, Knut Erik Tollefsen
Many environmental matrices contaminated with organic pollutants derived from crude oil or degraded petroleum contain mixtures so complex that they are typically unresolved by conventional analytical techniques such as gas chromatography. The resulting chromatographic features have become known as 'humps' or unresolved complex mixtures (UCMs). These UCMs often dominate the organic contaminants of polluted environmental samples: for example, in oil sands produced water up to 150mgL(-1) of 'naphthenic acids' appear as UCMs when examined by gas chromatography as the esters...
September 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#13
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar Deep Sharma, Michael Ott, Tobias Cantz
The quest for physiologically active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC)-derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided...
October 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28683306/ror%C3%AE-induces-klf4-mediated-m2-polarization-in-the-liver-macrophages-that-protect-against-nonalcoholic-steatohepatitis
#14
Yong-Hyun Han, Hyeon-Ji Kim, Hyelin Na, Min-Woo Nam, Ju-Yeon Kim, Jun-Seok Kim, Seung-Hoi Koo, Mi-Ock Lee
The regulation of M1/M2 polarization in liver macrophages is closely associated with the progression of nonalcoholic steatohepatitis (NASH); however, the mechanism involved in this process remains unclear. Here, we describe the orphan nuclear receptor retinoic-acid-related orphan receptor α (RORα) as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. RORα enhanced M2 polarization in KCs by inducing the kruppel-like factor 4. M2 polarization was defective in KCs and bone-marrow-derived macrophages of the myeloid-specific RORα null mice, and these mice were susceptible to HFD-induced NASH...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28659476/entry-and-release-of-hepatitis-c-virus-in-polarized-human-hepatocytes
#15
Sandrine Belouzard, Adeline Danneels, Lucie Fénéant, Karin Séron, Yves Rouillé, Jean Dubuisson
Hepatitis C virus (HCV) infects primarily hepatocytes that are highly polarized cells. The relevance of cell polarity in the HCV life cycle has only been addressed in distant models and remains poorly understood. Although polarized epithelial cells have a rather simple morphology with a basolateral and an apical domain, hepatocytes exhibit complex polarization structures. However, it has been reported that some selected polarized HepG2 cell clones can exhibit a honeycomb pattern of distribution of the tight-junction proteins, typical of columnar polarized epithelia which can be used as a simple model to study the role of cell polarization in viral infection of hepatocytes...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28640790/microrna-155-deficiency-in-kupffer-cells-ameliorates-liver-ischemia-reperfusion-injury-in-mice
#16
Yakun Li, Dongxia Ma, Zhimin Wang, Jun Yang
BACKGROUND: MicroRNA-155 (miR-155) is known to be involved in autoimmune diseases, inflammation, and transplantation. However, its role in a warm hepatic ischemia-reperfusion (IR) model has not been fully elucidated. METHODS: Partial hepatic IR was performed in wild-type and miR-155-deficient mice treated with or without GdCl3, and then the serum transaminase concentration and histology were analyzed. Kupffer cells (KCs) were isolated from the liver after IR, and immunohistochemistry was used to evaluate activation and polarization...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28596109/cytotherapy-with-m1-polarized-macrophages-ameliorates-liver-fibrosis-by-modulating-immune-microenvironment-in-mice
#17
Peng-Fei Ma, Chun-Chen Gao, Jing Yi, Jun-Long Zhao, Shi-Qian Liang, Yang Zhao, Yu-Chen Ye, Jian Bai, Qi-Jun Zheng, Ke-Feng Dou, Hua Han, Hong-Yan Qin
BACKGROUND & AIMS: Macrophages play vital roles in chronic liver injury, and have been tested as a tool for cytotherapy in liver fibrosis. However, macrophages possess ontogenic and functional heterogeneities. Some subsets are pro-fibrotic, whereas others are anti-fibrotic. This study aimed to clarify which macrophage subset is efficient for cytotherapy in liver fibrosis and to elucidate the underlying mechanisms. METHODS: Liver fibrosis was induced in mice by carbon tetrachloride injection or bile duct ligation...
July 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28542148/modulation-of-liver-regeneration-via-myeloid-pten-deficiency
#18
Wen-Tao Ma, Yan-Jie Jia, Qing-Zhi Liu, Yan-Qing Yang, Jing-Bo Yang, Zhi-Bin Zhao, Zhen-Ye Yang, Qing-Hua Shi, Hong-Di Ma, M Eric Gershwin, Zhe-Xiong Lian
Molecular mechanisms that modulate liver regeneration are of critical importance for a number of hepatic disorders. Kupffer cells and natural killer (NK) cells are two cell subsets indispensable for liver regeneration. We have focused on these two populations and, in particular, the interplay between them. Importantly, we demonstrate that deletion of the myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) leading to an M2-like polarization of Kupffer cells, which results in decreased activation of NK cells...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28519899/hepatic-aa-amyloidosis-in-a-cat-cytologic-and-histologic-identification-of-aa-amyloid-in-macrophages
#19
Sakurako Neo-Suzuki, Takayuki Mineshige, Junichi Kamiie, Hideki Kayanuma, Yukako Mochizuki, Masaharu Hisasue, Ryo Tsuchiya, Kinji Shirota
A 3-year-old, spayed female, Domestic Shorthair cat presented with anorexia, lethargy, vomiting, probable hemoabdomen, and multiple masses on the right lateral liver lobe. Clinicopathologic and imaging abnormalities included anemia, azotemia, icterus, and hepatomegaly with hypoechoic masses. On cytologic evaluation of a fine-needle aspiration of a liver mass there was abundant extracellular pink- to purple-colored material between hepatocytes. The amorphous material was stained with direct fast scarlet (DFS), and green birefringent areas were observed under polarized light, confirming the presence of amyloid...
June 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28500084/bisphenol-a-promotes-hepatic-lipid-deposition-involving-kupffer-cells-m1-polarization-in-male-mice
#20
Qiong Lv, Rufei Gao, Chuan Peng, Juan Yi, Lulu Liu, Shumin Yang, Danting Li, Jinbo Hu, Ting Luo, Mei Mei, Ying Song, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Bisphenol A (BPA), one of the most common environmental endocrine disruptors, is considered to promote hepatic lipid deposition. However, the mechanism has not been fully elucidated. The polarization of Kupffer cells (KCs) plays an important role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs), which contributes to dysregulated lipid metabolism. The purpose of this study is to investigate the role of KC polarization in BPA-induced hepatosteatosis in male mice. In this study, we examined hepatic lipid contents and quantified M1KC in BPA-treated CD1 mice, and further explored the interaction between KCs and hepatocytes using conditional HepG2 cell culture...
August 2017: Journal of Endocrinology
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