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| 1 | Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis显示文摘AIM: To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease (IBD). METHODS: To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis (UC) and Crohn’s disease (CD) compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed. RESULTS: We could show that aquaporin-8 (AQP8) mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQP8, however, revealed no mutations or polymorphisms in IBD patients. CONCLUSION: Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic infla- mmation and ulceration. | Alexandra Zahn Christoph Moehle Thomas Langmann Robert Ehehalt Frank Autschbach Wolfgang Stremmel Gerd Schmitz | 2007 | World Journal of Gastroenterology2007，13，11： | 13 |
| 2 | Exogenous sphingomyelinase causes impaired intestinal epithelial barrier function显示文摘AIM: To test the hypothesis that hydrolysis of sphingomyelin to ceramide changes the composition of tight junctions (TJs) with increasing permeability of the intestinal epithelium. METHODS: Monolayers of Caco-2 cells were used as an in vitro model for the intestinal barrier. Permeability was determined by quantifi cation of transepithelialflux and transepithelial resistance. Sphingolipid-rich membrane microdomains were isolated by a discontinuous sucrose gradient and characterized by Western-blot. Lipid content of microdomains was analysed by tandem mass spectrometry. Ceramide was subcellularly localized by immunofluorescent staining.RESULTS: Exogenous sphingomyelinase increased transepithelial permeability and decreased transepithelial resistance at concentrations as low as 0.01 U/mL. Lipid analysis showed rapid accumulation of ceramide in the membrane fractions containing occludin and claudin-4, representing TJs. In these fractions we observed a concomitant decrease of sphingomyelin and cholesterol with increasing concentrations of ceramide. Immunofluorescent staining confirmed clustering of ceramide at the sites of cell-cell contacts. Neutralization of surface ceramide prevented the permeability-increase induced by platelet activating factor. CONCLUSION: Our findings indicate that changes in lipid composition of TJs impair epithelial barrier functions. Generation of ceramide by sphingomyelinases might contribute to disturbed barrier function seen in diseases such as inflammatory, infectious, toxic or radiogenic bowel disease. | Jürgen Bock Gerhard Liebisch Joachim Schweimer Gerd Schmitz Gerhard Rogler | 2007 | World Journal of Gastroenterology2007，13，39： | 11 |
| 3 | Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro显示文摘AIM: Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD).METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model.RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinA1,we found abundantly co-expressed EphB2 and ephrin-B1/2.Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrinB1/2 expressing rat IEC-6-cells with recombinant EphB1Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge.CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD. | Christian Hafner Stefanie Meyer Thomas Langmann Gerd Schmitz Frauke Bataille Ilja Hagen Bernd Becker Alexander Roesch Gerhard Rogler Michael Landthaler Thomas Vogt | 2005 | World Journal of Gastroenterology2005，11，26： | 9 |
| 4 | Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inlammatory bowel disease显示文摘AIM:To determine free and conjugated serum bile acid (BA) levels in in? ammatory bowel disease (IBD) subgroups with defi ned clinical manifestations.METHODS: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy controls by liquid chromatography coupled to electrospray ionization tandem mass spectrometry.RESULTS: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the secondary BA lithocholic acid (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis (UC), while most other serum BA species were decreased significantly. Total BA, total BA conjugate, and total BA glycoconjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as significantly increased as the secondary BAs LCA, ursodeoxycholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode-oxycholic acid, were increased significantly compared to controls and patients without surgical interventions.CONCLUSION: Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diagnostic characterization and differentiation of IBD subgroups with defined clinical manifestations. | Carsten Gnewuch Gerhard Liebisch Thomas Langmann Benjamin Dieplinger Thomas Mueller Meinhard Haltmayer Hans Dieplinger Alexandra Zahn Wolfgang Stremmel Gerhard Rogler Gerd Schmitz | 2009 | World Journal of Gastroenterology2009，15，25： | 4 |
| 5 | Lithocholic acid induction of the FGF19 promoter in intestinal cells is mediated by PXR显示文摘AIM: To study the effect of the toxic secondary bile acid lithocholic acid (LCA) on the expression of fibroblast growth factor 19 (FGF19) in intestinal cells and to characterize the pregnane-X-receptor (PXR) response of the FGF19 promoter region. METHODS: The intestinal cell line LS174T was stimulated with various concentrations of chenodeoxy-cholic acid and lithocholic acid for several time points. FGF19 mRNA levels were determined with quantitative realtime RT-PCR. FGF19 deletion promoter constructs were generated and the LCA response was analzyed in reporter assays. Co-transfections with PXR and RXR were carried out to study FGF19 regulation by these factors. RESULTS: LCA and CDCA strongly up-regulate FGF19 mRNA expression in LS174T cells in a time and dose dependent manner. Using reporter gene assays with several deletion constructs we found that the LCA responsive element in the human FGF19 promoter maps to the proximal regulatory region containing two poten-tial binding sites for PXR. Overexpression of PXR and its dimerization partner retinoid X receptor (RXR) and stimulation with LCA or the potent PXR ligand rifampicin leads to a signifi cant induction of FGF19 promoter activ-ity in intestinal cells. CONCLUSION: LCA induced feedback inhibition of bile acid synthesis in the liver is likely to be regulated by PXR inducing intestinal FGF19 expression. | Wolfgang Wistuba Carsten Gnewuch Gerhard Liebisch Gerd Schmitz Thomas Langmann | 2007 | World Journal of Gastroenterology2007，13，31： | 4 |
| 6 | Mathematical Zero-Inertia Modeling of Surface Irrigation:Advance in Borders显示文摘 | Gerd H Schmitz Gunther J | 1990 | Journal of Irrigation and Drainage Engineering ASCE1990，116，5： | 1 |
| 7 | Frequency and significance of pro12Ala and Pro115Gln polymorphism in gene for peroxisome proliferation-activated receptor-γ2 regarding metabolic parameters in a caucasian cohortregarding metabolic parameters in a caucasian cohort显示文摘 | Andreas Sch?ffler Nicole Barth Gerd Schmitz Bettina Ziets Klaus-Dieter Palitzsch Jürgen Sch?lmerich | 2001 | Endocrine2001，，3： | 1 |
| 8 | High-speed apolip-oprotein E genotyping and apolipoprotein B3500 mutation detection using real-time fluorescence PCR and melting curves显示文摘 | Charalampos Aslarfidis Gerd Schmitz | 1999 | Clin Chem1999，45，： | 1 |
| 9 | A rapid GC-MS method for quantification of positional and geometric isomers of fatty acid methyl esters 显示文摘 | Josef Ecker MaxScherer Gerd Schmitz Gerhard Liebisch | 2012 | Journal of Chromatography B2012，897，15： | 1 |
| 10 | The opposing effects of n - 3 and n - 6 fatty acids 显示文摘 | Gerd Schmitz Josef Ecker | 2008 | Progress in Lipid Reseaxch2008，47，： | 1 |
| 11 | Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis显示文摘 | Hisashi Kubota Hideyuki Ishihara Thomas Langmann Gerd Schmitz Bruno Stieger Heinz-Gregor Wieser Yasuhiro Yonekawa Karl Frei | 2005 | Epilepsy Research2005，，3： | 1 |
| 12 | Differential gene expression of Eph receptors and Ephrins in benign human tissues and cancers显示文摘 | Christian Hafner Gerd Schmitz Stefanie Meyer | 2004 | Clin Chem2004，50，3： | 1 |
| 13 | Common variants in the gene encoding ATP-binding cassette transporter 1 in men with low HDL cholesterol levels and coronary heart disease显示文摘 | Margaret E. Brousseau Marek Bodzioch Ernst J. Schaefer Allison L. Goldkamp Danuta Kielar Mario Probst Jose M. Ordovas Charalampos Aslanidis Karl J. Lackner Hanna Bloomfield Rubins Dorothea Collins Sander J. Robins Peter W.F. Wilson Gerd Schmitz | 2001 | Atherosclerosis2001，，： | 1 |
| 14 | Molecular Cloning of the Human ATP-Binding Cassette Transporter 1 (hABC1): Evidence for Sterol-Dependent Regulation in Macrophages显示文摘 | Thomas Langmann Jochen Klucken Markus Reil Gerhard Liebisch Marie-Fran?oise Luciani Giovanna Chimini Wolfgang E. Kaminski Gerd Schmitz | 1999 | Biochemical and Biophysical Research Communications1999，，1： | 1 |
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