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https://www.readbyqxmd.com/read/28445529/ductular-reaction-correlates-with-fibrogenesis-but-does-not-contribute-to-liver-regeneration-in-experimental-fibrosis-models
#1
András Rókusz, Dániel Veres, Armanda Szücs, Edina Bugyik, Miklós Mózes, Sándor Paku, Péter Nagy, Katalin Dezső
BACKGROUND AND AIMS: Ductular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis-ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models. METHODS: Liver fibrosis/cirrhosis was induced in wild type and TGFβ overproducing transgenic mice by carbon tetrachloride and thioacetamide administration...
2017: PloS One
https://www.readbyqxmd.com/read/28416441/glechoma-hederacea-extracts-attenuate-cholestatic-liver-injury-in-a-bile-duct-ligated-rat-model
#2
Ya-Yu Wang, Shih-Yi Lin, Wen-Ying Chen, Su-Lan Liao, Chih-Cheng Wu, Pin-Ho Pan, Su-Tze Chou, Chun-Jung Chen
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. AIM OF THE STUDY: This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. MATERIALS AND METHODS: Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats...
April 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28348420/reelin-expression-in-human-liver-of-patients-with-chronic-hepatitis-c-infection
#3
Simone Carotti, Giuseppe Perrone, Michelina Amato, Umberto Vespasiani Gentilucci, Daniela Righi, Maria Francesconi, Claudio Pellegrini, Francesca Zalfa, Maria Zingariello, Antonio Picardi, Andrea Onetti Muda, Sergio Morini
Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV). On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis...
March 17, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28287574/isolation-and-enrichment-of-liver-progenitor-subsets-identified-by-a-novel-surface-marker-combination
#4
Henrike Julich-Haertel, Marina Tiwari, Christina Mehrfeld, Elmar Krause, Miroslaw Kornek, Veronika Lukacs-Kornek
During chronic liver injuries, progenitor cells expand in a process called ductular reaction, which also entails the appearance of inflammatory cellular infiltrate and epithelial cell activation. The progenitor cell population during such inflammatory reactions has mostly been investigated using single surface markers, either by histological analysis or by flow cytometry-based techniques. However, novel surface markers identified various functionally distinct subsets within the liver progenitor/stem cell compartment...
February 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28276299/immunohistochemical-analysis-of-the-stem-cell-marker-lgr5-in-pediatric-liver-disease
#5
Zahida Khan, Anne Orr, George K Michalopoulos, Sarangarajan Ranganathan
Aims In regenerating liver, hepatic progenitor cells (HPCs) are recruited in response to injury; however, few highly specific human HPC markers exist for the hepatocyte lineage. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a Wnt-associated stem cell marker, has been extensively studied in intestinal stem cells, but little is known about its expression in human liver. We hypothesized that LGR5+ HPCs are induced in the regenerative response to pediatric liver injury. Methods and results Immunohistochemistry was used to characterize LGR5 expression in pediatric liver explants (n = 36)...
January 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28249257/therapeutic-mechanisms-of-bile-acids-and-nor-ursodeoxycholic-acid-in-non-alcoholic-fatty-liver-disease
#6
Daniel Steinacher, Thierry Claudel, Michael Trauner
Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28187190/widespread-gli-expression-but-limited-canonical-hedgehog-signaling-restricted-to-the-ductular-reaction-in-human-chronic-liver-disease
#7
Candice Alexandra Grzelak, Nicholas David Sigglekow, Janina Elke Eleonore Tirnitz-Parker, Elizabeth Jane Hamson, Alessandra Warren, Bharvi Maneck, Jinbiao Chen, Bramilla Patkunanathan, Jade Boland, Robert Cheng, Nicholas Adam Shackel, Devanshi Seth, David Geoffrey Bowen, Luciano Gastón Martelotto, D Neil Watkins, Geoffrey William McCaughan
Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations...
2017: PloS One
https://www.readbyqxmd.com/read/28150744/engineering-an-endocrine-neo-pancreas-by-repopulation-of-a-decellularized-rat-pancreas-with-islets-of-langerhans
#8
H Napierala, K-H Hillebrandt, N Haep, P Tang, M Tintemann, J Gassner, M Noesser, H Everwien, N Seiffert, M Kluge, E Teegen, D Polenz, S Lippert, D Geisel, A Reutzel Selke, N Raschzok, A Andreou, J Pratschke, I M Sauer, B Struecker
Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104292/hepatic-prominin-1-expression-is-associated-with-biliary-fibrosis
#9
Marie V Nguyen, Jessica A Zagory, William H Dietz, Alex Park, Michael Fenlon, Menghan Zhao, Jiabo Xu, Ingrid Lua, Nirmala Mavila, Kinji Asahina, Kasper S Wang
BACKGROUND: Intrahepatic biliary fibrosis, as seen with cholestatic liver injuries such as biliary atresia, is mechanistically distinct from fibrosis caused by hepatocyte toxicity. We previously demonstrated the expansion of cells expressing the stem/progenitor cell marker Prominin-1, within regions of developing fibrosis in biliary atresia. Thus, we hypothesized that Prominin-1 expression is biliary fibrosis-specific. METHODS: Gene expression of Prominin-1 was analyzed in adult mice undergoing either cholestatic bile duct ligation or hepatotoxic carbon tetrachloride administration by quantitative polymerase chair reaction...
May 2017: Surgery
https://www.readbyqxmd.com/read/28098217/disrupting-hepatocyte-cyp51-from-cholesterol-synthesis-leads-to-progressive-liver-injury-in-the-developing-mouse-and-decreases-rorc-signalling
#10
Žiga Urlep, Gregor Lorbek, Martina Perše, Jera Jeruc, Peter Juvan, Madlen Matz-Soja, Rolf Gebhardt, Ingemar Björkhem, Jason A Hall, Richard Bonneau, Dan R Littman, Damjana Rozman
Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (H(Cyp51-/-)) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#11
Rikke K Kirk, Charles Pyke, Matthias G von Herrath, Jane P Hasselby, Lars Pedersen, Pia G Mortensen, Lotte B Knudsen, Ken Coppieters
AIMS: Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of type 2 diabetes (T2D). Immunohistochemical studies for GLP-1R expression have been hampered previously by the use of unspecific polyclonal antibodies. This study aimed to assess the expression levels of GLP-1R in a set of T2D donor samples obtained via nPOD...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28079599/steatohepatitis-like-changes-in-focal-nodular-hyperplasia-a-finding-to-distinguish-from-steatohepatitic-variant-of-hepatocellular-carcinoma
#12
Kemal Deniz, Roger K Moreira, Matthew M Yeh, Linda D Ferrell
Steatohepatitis-like change has not been described in focal nodular hyperplasia (FNH). Steatohepatitis-like change in FNH may show overlapping features with steatohepatitic variant of hepatocellular carcinoma (HCC). This problem can be compounded if seen in FNH with widened cell plates or hepatocyte rosettes, other features that can also be seen in HCC. This study examined steatotic FNHs for the frequency of steatohepatitis-like change, especially in the setting of FNH with rosettes and/or widened cell plates...
February 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28073888/selective-targeting-of-lysyl-oxidase-like-2-loxl2-suppresses-hepatic-fibrosis-progression-and-accelerates-its-reversal
#13
Naoki Ikenaga, Zhen-Wei Peng, Kahini A Vaid, Susan B Liu, Shuhei Yoshida, Deanna Y Sverdlov, Amanda Mikels-Vigdal, Victoria Smith, Detlef Schuppan, Yury V Popov
BACKGROUND/AIMS: We studied the role of lysyl oxidase-like 2 (LOXL2) in collagen crosslinking and hepatic progenitor cell (HPC) differentiation, and the therapeutic efficacy of a LOXL2-blocking monoclonal antibody on liver fibrosis progression/reversal in mice. METHODS: Anti-LOXL2 antibody, control antilysyl oxidase antibody or placebo was administered during thioacetamide (TAA)-induced fibrosis progression or during recovery. Therapeutic efficacy in biliary fibrosis was tested in BALB/c...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28051157/progressive-induction-of-hepatocyte-progenitor-cells-in-chronically-injured-liver
#14
Naoki Tanimizu, Norihisa Ichinohe, Masahiro Yamamoto, Haruhiko Akiyama, Yuji Nishikawa, Toshihiro Mitaka
Differentiated epithelial cells show substantial lineage plasticity upon severe tissue injuries. In chronically injured mouse livers, part of hepatocytes become Sry-HMG box containing 9 (Sox9) (+) epithelial cell adhesion molecule (-) hepatocyte nuclear factor 4 α (+) biphenotypic hepatocytes. However, it is not clear whether all Sox9(+) hepatocytes uniformly possess cellular properties as hepatocyte progenitors. Here, we examined the microarray data comparing Sox9(+) hepatocytes with mature hepatocytes and identified CD24 as a novel marker for biphenotypic hepatocytes...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28013213/environmental-xenoestrogens-super-activate-a-variant-murine-er-beta-in-cholangiocytes
#15
Stephanie K Meyer, Philip M E Probert, Anne K Lakey, Alastair C Leitch, Lynsay I Blake, Paul A Jowsey, Martin P Cooke, Peter G Blain, Matthew C Wright
High systemic levels of oestrogens are cholestatic and primary biliary cholangitis (PBC)-which is characterized by hepatic ductular inflammation-is thought to be triggered by exposure to xenobiotics such as those around landfill sites. Xenoestrogens may be a component of this chemical trigger. We therefore hypothesized that xenoestrogens are present at higher levels in the proximity of landfill sites. To test this hypothesis, soil samples were collected, extracts prepared and biological oestrogenic activity examined using cell-based reporter gene assays...
March 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27989788/distinction-between-inflammatory-hepatocellular-adenoma-and-mass-effect-on-liver-sampling
#16
Diana Agostini-Vulaj, Ashwani K Sharma, Jennifer J Findeis-Hosey, Loralee A McMahon, Raul S Gonzalez
Inflammatory hepatocellular adenoma (IHA) is characterized by sinusoidal dilation, inflammation, and bile ductular reaction. However, these changes can also be seen in non-neoplastic liver tissue adjacent to a mass lesion. This differential may arise in biopsy tissue attempting to sample a liver mass. Serum amyloid A (SAA) immunostaining is useful for the diagnosis of IHA but is not entirely specific. Additionally, the histologic pattern of mass effect (ME) has received little formal scrutiny. We compared the clinical, morphologic, and immunohistochemical findings in 18 IHA and 36 livers with ME...
December 15, 2016: Human Pathology
https://www.readbyqxmd.com/read/27938504/knockdown-of-mir-23-mir-27-and-mir-24-alters-fetal-liver-development-and-blocks-fibrosis-in-mice
#17
Charles E Rogler, Joe S Matarlo, Brian Kosmyna, Daniel Fulop, Leslie E Rogler
MicroRNAs (miRNAs) regulate cell fate selection and cellular differentiation. miRNAs of the miR23b polycistron (miR-23b, miR-27b, and miR-24) target components of the TGF-β signaling pathway and affect murine bile ductular and hepatocyte cell fate selection in vitro. Here we show that miR-23b polycistron miRNAs directly target murine Smad4, which is required for TGF-β signaling. Injection of antagomirs against these miRNAs directly into E16.5 murine fetuses caused increased cytokeratin expression in sinusoids and primitive ductular elements throughout the parenchyma of newborn mice...
February 10, 2017: Gene Expression
https://www.readbyqxmd.com/read/27936185/hedgehog-signaling-overcomes-an-ezh2-dependent-epigenetic-barrier-to-promote-cholangiocyte-expansion
#18
Nidhi Jalan-Sakrikar, Thiago M De Assuncao, Jie Lu, Luciana L Almada, Gwen Lomberk, Martin E Fernandez-Zapico, Raul Urrutia, Robert C Huebert
BACKGROUND & AIMS: Developmental morphogens play an important role in coordinating the ductular reaction and portal fibrosis occurring in the setting of cholangiopathies. However, little is known about how membrane signaling events in ductular reactive cells (DRCs) are transduced into nuclear transcriptional changes to drive cholangiocyte maturation and matrix deposition. Therefore, the aim of this study was to investigate potential mechanistic links between cell signaling events and epigenetic regulators in DRCs...
2016: PloS One
https://www.readbyqxmd.com/read/27918111/imatinib-accelerates-progenitor-cell-mediated-liver-regeneration-in-choline-deficient-ethionine-supplemented-diet-fed-mice
#19
András Rókusz, Edina Bugyik, Vanessza Szabó, Armanda Szücs, Sándor Paku, Péter Nagy, Katalin Dezső
Severe chronic hepatic injury can induce complex reparative processes. Ductular reaction and the appearance of small hepatocytes are standard components of this response, which is thought to have both adverse (e.g. fibrosis, carcinogenesis) and beneficial (regeneration) consequences. This complex tissue reaction is regulated by orchestrated cytokine action. We have investigated the influence of the tyrosine kinase inhibitor imatinib on a regenerative process. Ductular reaction was induced in mice by the widely used choline-deficient ethionine-supplemented diet (CDE)...
October 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27881141/analysis-of-epithelial-mesenchymal-transition-markers-in-the-histogenesis-of-hepatic-progenitor-cell-in-hbv-related-liver-diseases
#20
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
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