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Hepatocyte polarity

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https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#1
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
#2
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
#3
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
#4
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
#5
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar D 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...
July 12, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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-cell-m1-polarization-in-male-mice
#12
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), as one of the most common environmental endocrine disruptors, is considered to promote hepatic lipid deposition, but the mechanisms 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 by using conditional HepG2 cell culture...
May 12, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#13
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most-DILI-concern and 55 of No-DILI-concern)...
May 15, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28333715/noninvasive-imaging-of-stored-red-blood-cell-transfusion-aggravating-sepsis-induced-liver-injury-associated-with-increased-activation-of-m1-polarized-kupffer-cells
#14
Tao Wu, Lei Wang, Jie An, Chao Y Wu, Yue Wang, Lu Qian, Jun Zhou, Yu L Zhang, Qian Q Zhou, Xiao H Wang, Hua F Wang, Qiu X Fu, Lin S Zhan
Liver injury has a critical effect on the severity and outcome of sepsis. The impact of stored RBCs on the pathogenesis of sepsis-associated hepatic injury is not well understood. Therefore, to investigate the effects of stored-RBC transfusion on sepsis-induced liver damage as well as the associated mechanism, we constructed a sepsis mouse model enabling non-invasive imaging of bacterial infection caused by Pseudomonas aeruginosa, a common gram-negative respiratory pathogen. We showed that transfusions with stored RBCs enhanced sepsis-induced liver injury in vivo, and liver injury exacerbated the severity of sepsis and decreased survival in P...
March 22, 2017: Shock
https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#15
Michal Pyzik, Timo Rath, Timothy T Kuo, Sanda Win, Kristi Baker, Jonathan J Hubbard, Rosa Grenha, Amit Gandhi, Thomas D Krämer, Adam R Mezo, Zachary S Taylor, Kevin McDonnell, Vicki Nienaber, Jan Terje Andersen, Atsushi Mizoguchi, Laurence Blumberg, Shalaka Purohit, Susan D Jones, Greg Christianson, Wayne I Lencer, Inger Sandlie, Neil Kaplowitz, Derry C Roopenian, Richard S Blumberg
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28323124/cd44-is-a-key-player-in-non-alcoholic-steatohepatitis
#16
Stéphanie Patouraux, Déborah Rousseau, Stéphanie Bonnafous, Cynthia Lebeaupin, Carmelo Luci, Clémence M Canivet, Anne-Sophie Schneck, Adeline Bertola, Marie-Christine Saint-Paul, Antonio Iannelli, Jean Gugenheim, Rodolphe Anty, Albert Tran, Béatrice Bailly-Maitre, Philippe Gual
BACKGROUND & AIMS: Cluster of differentiation (CD)44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. We aimed to evaluated the contribution of CD44 to non-alcoholic steatohepatitis (NASH) development and liver injury in mouse models and in patients at various stages of non-alcoholic fatty liver disease (NAFLD) progression...
March 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28272754/hyperpolarized-%C3%AE-1-13-c-gluconolactone-as-a-probe-of-the-pentose-phosphate-pathway
#17
Karlos X Moreno, Crystal E Harrison, Matthew E Merritt, Zoltan Kovacs, Craig R Malloy, A Dean Sherry
The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis), but simple methods for detecting changes in flux through this pathway are not available. MRI of hyperpolarized (13) C-enriched metabolites offers considerable potential as a rapid, non-invasive tool for detecting changes in metabolic fluxes. In this study, hyperpolarized δ-[1-(13) C]gluconolactone was used as a probe to detect flux through the oxidative portion of the pentose phosphate pathway (PPPox ) in isolated perfused mouse livers...
June 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28272428/secreted-ectodomain-of-siglec-9-and-mcp-1-synergistically-improve-acute-liver-failure-in-rats-by-altering-macrophage-polarity
#18
Takanori Ito, Masatoshi Ishigami, Yoshihiro Matsushita, Marina Hirata, Kohki Matsubara, Tetsuya Ishikawa, Hideharu Hibi, Minoru Ueda, Yoshiki Hirooka, Hidemi Goto, Akihito Yamamoto
Effective treatments for acute liver failure (ALF) are still lacking. We recently reported that a single intravenous administration of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) into the D-galactosamine (D-Gal)-induced rat ALF model improves the liver injury. However, the specific factors in SHED-CM that are responsible for resolving ALF remain unclear. Here we found that depleting SHED-CM of two anti-inflammatory M2 macrophage inducers-monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9)-abolished its ability to resolve rat ALF...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28267621/targeting-hepatic-macrophages-to-treat-liver-diseases
#19
REVIEW
Frank Tacke
Our view on liver macrophages in the context of health and disease has been reformed by the recognition of a remarkable heterogeneity of phagocytes in the liver. Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Kupffer cells are self-renewing, resident and principally non-migratory phagocytes, serving as sentinels for liver homeostasis. Liver injury triggers Kupffer cell activation, leading to inflammatory cytokine and chemokine release. This fosters the infiltration of monocytes into the liver, which give rise to large numbers of inflammatory monocyte-derived macrophages...
March 4, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28266877/glucuronidation-driving-factors-and-their-impact-on-glucuronide-disposition
#20
Guangyi Yang, Shufan Ge, Rashim Singh, Sumit Basu, Katherine Shatzer, Ming Zen, Jiong Liu, Yifan Tu, Chenning Zhang, Jinbao Wei, Jian Shi, Lijun Zhu, Zhongqiu Liu, Yuan Wang, Song Gao, Ming Hu
Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances. Although it is usually the secondary metabolic pathway for a compound preceded by phase I hydroxylation, glucuronidation alone could serve as the dominant metabolic pathway for many compounds, including some with high aqueous solubility. Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases (UGTs) into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters...
May 22, 2017: Drug Metabolism Reviews
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