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| 1 | 肠的障碍: 分子的小径和修饰词显示文摘 The gastrointestinal tract is frequently challenged by pathogens/antigens contained in food and water and the intestinal epithelium must be capable of rapid regeneration in the event of tissue damage. Disruption of the intestinal barrier leads to a number of immune-mediated diseases, including inflammatory bowel disease, food allergy, and celiac disease. The intestinal mucosa is composed of different types of epithelial cells in specific barrier functions. Epithelial cells control surfaceassociated bacterial populations without disrupting the intestinal microflora that is crucial for host health. They are also capable of modulating mucosal immune system, and are thus essential in maintaining homeostasis in the gut. Thus, the regulation of intestinal epithelial homeostasis is crucial for the maintenance of the structure of the mucosa and the defensive barrier functions. Recent studies have demonstrated that multiple molecular pathways are involved in the regulation of intestinal epithelial cell polarity. These include the Wnt, Notch, Hippo, transforming growth factor-β(TGF-β)/bone morphogenetic protein(BMP) and Hedgehog pathways, most of which were identified in lower organisms where they play important roles during embryogenesis. These pathways are also used in adult organisms to regulate multiple self-renewing organs. Understanding the interactions between these molecular mechanisms and intestinal barrier function will therefore provide important insight into the pathogenesis of intestinal-based immune-mediated diseases. | Min Kyung Jeon Christina Klaus Elke Kaemmerer Nikolaus Gassler | 2013 | World Journal of Gastrointestinal Pathophysiology2013，4，4： | 10 |
| 2 | Paneth cells in intestinal physiology and pathophysiology显示文摘Small intestinal mucosa is characterised by villus forming connective tissues with highly specialised surface lining epithelial cells essentially contributing to the establishment of the intestinal border.In order to perform these diverse functions,spatially distinct compartments of epithelial differentiation are found along the crypt-villus axis,including Paneth cells as a highly specialised cell type.Paneth cells locate in crypts and assist undifferentiated columnar cells,called crypt base columnar cells,and rapidly amplifying cells in the regeneration of absorptive and secretory cell types.There is some evidence that Paneth cells are involved in the configuration and function of the stem cell zone as well as intestinal morphogenesis and crypt fission.However,the flow of Paneth cells to crypt bottoms requires strong Wnt signalling guided by EphB3 and partially antagonised by Notch.In addition,mature Paneth cells are essential for the production and secretion of antimicrobial peptides including α-defensins/cryptdins.These antimicrobials are physiologically involved in shaping the composition of the microbiome.The autophagy related 16-like 1(ATG16L1) is a genetic risk factor and is involved in the exocytosis pathway of Paneth cells as well as a linker molecule to PPAR signalling and lipid metabolism.There is evidence that injuries of Paneth cells are involved in the etiopathogenesis of different intestinal diseases.The review provides an overview of the key points of Paneth cell activities in intestinal physiology and pathophysiology. | Nikolaus Gassler | 2017 | World Journal of Gastrointestinal Pathophysiology2017，8，4： | 7 |
| 3 | Modulating effects of acyl-CoA synthetase 5-derived mitochondrial Wnt2B palmitoylation on intestinal Wnt activity显示文摘AIM:To investigate the role of acyl-CoA synthetase 5(ACSL5)activity in Wnt signaling in intestinal surface epithelia.METHODS:Several cell lines were used to investigate the ACSL5-dependent expression and synthesis of Wnt2B,a mitochondrially expressed protein of the Wnt signaling family.Wnt activity was functionally assessed with a luciferase reporter assay.ACSL5-related biochemical Wnt2B modifications were investigatedwith a modified acyl-exchange assay.The findings from the cell culture models were verified using an Apcmin/+mouse model as well as normal and neoplastic diseased human intestinal tissues.RESULTS:In the presence of ACSL5,Wnt2B was unable to translocate into the nucleus and was enriched in mitochondria,which was paralleled by a significant decrease in Wnt activity.ACSL5-dependent S-palmitoylation of Wnt2B was identified as a molecular reason for mitochondrial Wnt2B accumulation.In cell culture systems,a strong relation of ACSL5 expression,Wnt2B palmitoylation,and degree of malignancy were found.Using normal mucosa,the association of ACSL5 and Wnt2B was seen,but in intestinal neoplasias the mechanism was only rudimentarily observed.CONCLUSION:ACSL5 mediates antiproliferative activities via Wnt2B palmitoylation with diminished Wnt activity.The molecular pathway is probably relevant for intestinal homeostasis,overwhelmed by other pathways in carcinogenesis. | Christina Klaus Ursula Schneider Christian Hedberg Anke K Schütz Jürgen Bernhagen Herbert Waldmann Nikolaus Gassler Elke Kaemmerer | 2014 | World Journal of Gastroenterology2014，20，40： | 4 |
| 4 | Human intestinal acyl-CoA synthetase 5 is sensitive to the inhibitor triacsin C显示文摘AIM:To investigate whether human acyl-CoA synthetase 5(ACSL5) is sensitive to the ACSL inhibitor triacsin C.METHODS:The ACSL isoforms ACSL1 and ACSL5 from rat as well as human ACSL5 were cloned and recombinantly expressed as 6xHis-tagged enzymes.Ni 2+-affinity purified recombinant enzymes were assayed at pH 7.5 or pH 9.5 in the presence or absence of triacsin C.In addition,ACSL5 transfected CaCo2 cells and intestinal human mucosa were monitored.ACSL5 expression in cellular systems was verified using Western blot and immunofluorescence.The ACSL assay mix included TrisHCl(pH 7.4),ATP,CoA,EDTA,DTT,MgCl 2,[9,103 H] palmitic acid,and triton X-100.The 200 μL reaction was initiated with the addition of solubilized,purified recombinant proteins or cellular lysates.Reactions were terminated after 10,30 or 60 min of incubation with Doles medium.RESULTS:Expression of soluble recombinant ACSL proteins was found after incubation with isopropyl betaD-1-thiogalactopyranoside and after ultracentrifugation these were further purified to near homogeneity with Ni 2+-affinity chromatography.Triacsin C selectively and strongly inhibited recombinant human ACSL5 protein at pH 7.5 and pH 9.5,as well as recombinant rat ACSL1(sensitive control),but not recombinant rat ACSL5(insensitive control).The IC50 for human ACSL5 was about 10 μmol/L.The inhibitory triacsin C effect was similar for different incubation times(10,30 and 60 min) and was not modified by the N-or C-terminal location of the 6xHis-tag.In order to evaluate ACSL5 sensitivity to triacsin C in a cellular environment,stable human ACSL5 CaCo2 transfectants and mechanically dissected normal human intestinal mucosa with high physiological expression of ACSL5 were analyzed.In both models,ACSL5 peak activity was found at pH 7.5 and pH 9.5,corresponding to the properties of recombinant human ACSL5 protein.In the presence of triacsin C(25 μmol/L),total ACSL activity was dramatically diminished in human ACSL5 transfectants as well as in ACSL5-rich human intestinal mucosa.CONCLUSION:The data strongly indicate that human ACSL5 is sensitive to triacsin C and does not compensate for other triacsin C-sensitive ACSL isoforms. | Elke Kaemmerer Anne Peuscher Andrea Reinartz Christian Liedtke Ralf Weiskirchen Jürgen Kopitz Nikolaus Gassler | 2011 | World Journal of Gastroenterology2011，17，44： | 3 |
| 5 | Beta-7 integrin controls enterocyte migration in the small intestine显示文摘AIM:To hypothesize that beta-7 integrin affects cellularmigration of both,lymphocytes and enterocytes.METHODS:The nucleoside analog Brd U was ip injected in beta-7-deficient mice(C57BL/6-Itgbtmlcgn/J)of male gender and age-matched male C57BL/J J mice(wild type)4,20,or 40 h before analysis.The total small intestine was isolated,dissected,and used for morphometrical studies.Brd U-positive epithelial cells were numbered in at least 15 hemi-crypts per duodenum,jejunum,and ileum of each animal.The outer most Brd U-positive cell(cellmax)was determined per hemi-crypt,numerically documented,and statistically analysed.RESULTS:Integrins containing the beta-7-chain were exclusively expressed on leukocytes.In the small intestinal mucosa of beta-7 integrin-deficient mice the number of intraepithelial lymphocytes was drastically decreased.Moreover,the Peyer’s patches of beta-7integrin-deficient mice appeared hypoplastic.In beta-7integrin-deficient mice the location of cellmax was found in a higher position than it was the case for the controls.The difference was already detected at 4 h after Brd U application,but significantly increased with time(40 h after Brd U injection)in all small intestinal segments investigated,i.e.,duodenum,jejunum,and ileum.Migration of small intestinal enterocytes was different between the experimental groups measured by cellmax locations.CONCLUSION:The E-cadherin beta-7 integrin pathway probably controls migration of enterocytes within the small intestinal surface lining epithelial layer. | Elke Kaemmerer Paula Kuhn Ursula Schneider Thomas Clahsen Min Kyung Jeon Christina Klaus Julia Andruszkow Michael Hrer Sabine Ernst Angela Schippers Norbert Wagner Nikolaus Gassler | 2015 | World Journal of Gastroenterology2015，21，6： | 3 |
| 6 | Molecular classification of colorectal carcinomas:The genotype-to-phenotype relation显示文摘Colorectal carcinomas(CRCs)are frequently found in industrialized countries and lead to a high incidence of malignancy-related mortality.Defined by histomorphological features,CRCs and their pre-invasive lesions are quite heterogeneous.The underlying molecular mechanisms include genomic instability,genomic mutation of tumor suppressor genes or oncogenes,epigenetic changes,and the microRNA network.The molecular mechanisms are guided by repeated clonal selections.The genotype-to-phenotype relation is assumed to be the great challenge of cancer research and the development of effective targeted therapies.At present a strong genotype-to-phenotype relation is characterized only for a minority of CRCs.Consequently,the molecular characterization of CRCs is essential to interpret histological patterns and to identify prognostic groups as well as patients for targeted therapy. | Elke Kaemmerer Christina Klaus Min Kyung Jeon Nikolaus Gassler | 2013 | World Journal of Gastroenterology2013，19，45： | 2 |
| 7 | Intestinal acyl-CoA synthetase 5: Activation of long chain fatty acids and behind显示文摘The intestinal mucosa is characterized by a high complexity in terms of structure and functions and allows for a controlled demarcation towards the gut lumen.On the one hand it is responsible for pulping and selective absorption of alimentary substances ensuring the immunological tolerance,on the other hand it prevents the penetration of micro-organisms as well as bacterial outgrowth.The continuous regeneration of surface epithelia along the crypt-villus-axis in the small intestine is crucial to assuring these various functions.The core phenomena of intestinal epithelia regeneration comprise cell proliferation,migration,differentiation,and apoptosis.These partly contrarily oriented processes are molecularly balanced through numerous interacting signaling pathways like Wnt/β-catenin,Notch and Hedgehog,and regulated by various modifying factors.One of these modifiers is acyl-CoA synthetase 5(ACSL5).It plays a key role in de novo lipid synthesis,fatty acid degradation and membrane modifications,and regulates several intestinal processes,primarily through different variants of protein lipidation,e.g.,palmitoylation.ACSL5 was shown to interact with proapoptotic molecules,and besides seems to inhibit proliferation along the crypt-villus-axis.Because of its proapoptotic and antiproliferative characteristics it could be of significant relevance for intestinal homeostasis,cellular disorder and tumor development. | Christina Klaus Min Kyung Jeon Elke Kaemmerer Nikolaus Gassler | 2013 | World Journal of Gastroenterology2013，19，42： | 2 |
| 8 | Lipid-induced up-regulation of human acyl-CoA synthetase 5 promotes hepatocellular apoptosis显示文摘 | Andrea Reinartz Josef Ehling Andrea Leue Christian Liedtke Ursula Schneider Jürgen Kopitz Thomas Weiss Claus Hellerbrand Ralf Weiskirchen Ruth Knüchel Nikolaus Gassler | 2010 | BBA - Molecular and Cell Biology of Lipids2010，，9： | 2 |
| 9 | Regulation of Enterocyte Apoptosis by Acyl-CoA Synthetase 5 Splicing显示文摘 | Nikolaus Gassler Wilfried Roth Benjamin Funke Armin Schneider Frank Herzog Jens J.W. Tischendorf Kerstin Grund Roland Penzel Ignacio G. Bravo John Mariadason Volker Ehemann Jaromir Sykora Tobias L. Haas Henning Walczak Tom Ganten Hanswalter Zentgraf Peter | 2007 | Gastroenterology2007，，2： | 2 |
| 10 | Dexamethasone-induced cisplatin and gemcitabine resistance in lung carcinoma samples treated ex vivo显示文摘 | Gassler N Zhang C Wenger T | | 0，，06： | 1 |
| 11 | Transmyocardial laser revascularization histological features in human nonresponder myocardium 显示文摘 | Gassler N Wintzer HO Stubbe HM | 1997 | Circulation1997，95，2： | 1 |
| 12 | Transmyocardial laser revascularization:histological features in human nonresponder myocardium显示文摘 | Gassler N Wintzer HO Stubbe HM | 1997 | Circulation1997，95，2： | 1 |
| 13 | c-Met Confers Protection Against Chronic Liver Tissue Damage and Fibrosis Progression After Bile Duct Ligation in Mice显示文摘 | Arne Giebeler Mark V. Boekschoten Christian Klein Malgorzata Borowiak Carmen Birchmeier Nikolaus Gassler Hermann E. Wasmuth Michael Müller Christian Trautwein Konrad L. Streetz | 2009 | Gastroenterology2009，，1： | 1 |
| 14 | Aberrant cell cycle progression and endoreplication in regenerating livers of mice that lack a single E-type cyclin显示文摘 | Nevzorova YA Tschaharganeh D Gassler N | 2009 | Gastroenterology2009，137，2： | 1 |
| 15 | Mutations in the Dna K chaperone affecting interaction with the Dna J cochaperone显示文摘 | GASSLER C S BUCHBERGER A LAUFEN T | 1998 | Proc Natl Acad Sci USA1998，95，15： | 1 |
| 16 | Globalization and the information economy:challenges and opportunities for Africa 显示文摘 | Gassler R S | 2001 | Global Society2001，15，1： | 1 |
| 17 | Regulation of differential pro- and anti-apoptotie signaling by gIueocortieolds 显示文摘 | Herr I Gassler N Friess H | 2007 | Apoptosis2007，12，2： | 1 |
| 18 | Podocyte injury underlies the progression of focal segmental glomerulosclerosis in the fa/fa Zucker rat显示文摘 | Gassler N Elger M Kranzlin B | 2001 | Kidney Int2001，60，1： | 1 |
| 19 | Determination of 'Fat- max' with lh cycling protocols of constant load显示文摘 | Meyer T Gassler N Kindermann W | 2007 | Appl Physiol Nutr Metab2007，32，2： | 1 |
| 20 | c-Met Confers Protection Against Chronic Liver Tissue Damage and Fibrosis Progression After Bile Duct Ligation in Mice显示文摘 | Arne Giebeler Mark V. Boekschoten Christian Klein Malgorzata Borowiak Carmen Birchmeier Nikolaus Gassler Hermann E. Wasmuth Michael Müller Christian Trautwein Konrad L. Streetz | 2009 | Gastroenterology2009，，1： | 1 |
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