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| 1 | Transforming growth factor-β1 induces intestinal myofibroblast differentiation and modulates their migration显示文摘AIM:To investigate the effects of transforming growth factorβ1(TGF-β1)on the differentiation of colonic lamina propria fibroblasts(CLPF)into myofibroblasts in vitro. METHODS:Primary CLPF cultures were incubated with TGF-β1 and analyzed for production ofα-smooth muscle actin(α-SMA),fibronectin(FN)and FN isoforms.Migration assays were performed in a modified 48-well Boyden chamber.Levels of total and phosphorylated focal adhesion kinase(FAK)in CLPF were analyzed after induction of migration.RESULTS:Incubation of CLPF with TGF-β1 for 2 d did not changeα-SMA levels,while TGF-β1 treatment for 6 d significantly increasedα-SMA production. Short term incubation(6 h)with TGF-β1 enhanced CLPF migration,while long term treatment(6 d)of CLPF with TGF-β1 reduced migration to 15%-37% compared to untreated cells.FN and FN isoform mRNA expression were increased after short term incubation with TGF-β1(2 d)in contrast to long term incubation with TGF-β1 for 6 d.After induction of migration, TGF-β1-preincubated CLPF showed higher amounts of FN and its isoforms and lower levels of total and phosphorylated FAK than untreated cells. CONCLUSION:Long term incubation of CLPF with TGF-β1 induced differentiation into myofibroblasts with enhancedα-SMA,reduced migratory potential and FAK phosphorylation,and increased FN production.In contrast,short term contact(6 h)of fibroblasts with TGF-β1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction ofα-SMA production. | Julia Brenmoehl Sandra Nicole Miller Claudia Hofmann Daniela Vogl Werner Falk Jrgen Schlmerich Gerhard Rogler | 2009 | World Journal of Gastroenterology2009，15，12： | 12 |
| 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 | The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Definitions and diagnosis显示文摘 | Gert Van Assche Axel Dignass Julian Panes Laurent Beaugerie John Karagiannis Mathieu Allez Thomas Ochsenkühn Tim Orchard Gerhard Rogler Edouard Louis Limas Kupcinskas Gerassimos Mantzaris Simon Travis Eduard Stange | 2009 | Journal of Crohn’s and Colitis2009，，1： | 10 |
| 4 | 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 |
| 5 | Pathophysiology of fistula formation in Crohn's disease显示文摘Fistulae represent an important complication in patient suffering from Crohn's disease(CD). Cumulative incidence of fistula formation in CD patients is 17%-50% and about one third of patients suffer from recurring fistulae formation. Medical treatment options often fail and also surgery frequently is not successful. Available data indicate that CD-associated fistulae originate from an epithelial defect that may be caused by ongoing inflammation. Having undergone epithelial to mesenchymal transition(EMT), intestinal epithelial cells(IEC) penetrate into deeper layers of the mucosa and the gut wall causing localized tissue damage formation of a tube like structure and finally a connection to other organs or the body surface. EMT of IEC may be initially aimed toimprove wound repair mechanisms since 'conventional' wound healing mechanisms, such as migration of fibroblasts, are impaired in CD patients. EMT also enhances activation of matrix remodelling enzymes such as matrix metalloproteinase(MMP)-3 and MMP-9 causing further tissue damage and inflammation. Finally, soluble mediators like TNF and interleukin-13 further induce their own expression in an autocrine manner and enhance expression of molecules associated with cell invasiveness aggravating the process. Additionally, pathogen-associated molecular patterns also seem to play a role for induction of EMT and fistula development. Though current knowledge suggests a number of therapeutic options, new and more effective therapeutic approaches are urgently needed for patients suffering from CD-associated fistulae. A better understanding of the pathophysiology of fistula formation, however, is a prerequisite for the development of more efficacious medical anti-fistula treatments. | Michael Scharl Gerhard Rogler | 2014 | World Journal of Gastrointestinal Pathophysiology2014，5，3： | 5 |
| 6 | Use of thiopurines in inflammatory bowel disease显示文摘The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis.Nevertheless,many questions remain concerning the optimal treatment regimens of azathioprine,6-mercaptopurine and thioguanine.We will briefly summarize dose recommendations,indications for thiopurine therapy and side effects which are relevant in clinical practice.We discuss some currently debated topics,including the combination of azathioprine and allopurinol,switching of thiopurine therapy in case of side effects,the use of azathioprine in pregnancy,the infection risk using thiopurines and the evidence when to stop thiopurines.Excellent reviews have been published on the thiopurine metabolic pathway which will not be discussed here in detail. | Pascal Frei Luc Biedermann Ole Haagen Nielsen Gerhard Rogler | 2013 | World Journal of Gastroenterology2013，19，7： | 4 |
| 7 | 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 |
| 8 | Mucosal healing and deep remission: What does it mean?显示文摘The use of specific terms under different meanings and varying definitions has always been a source of confusion in science.When we point our efforts towards an evidence based medicine for inflammatory bowel diseases(IBD)the same is true:Terms such as'mucosal healing'or'deep remission'as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered.It appears to be useful to first have a look at the development of terms and their definitions,to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials.The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms.It may also lead to a better defined use of those terms for future studies.The terms'mucosal healing'and'deep remission'have been introduced in recent years as new therapeutic targets in the treatment of IBD patients.Several clinical trials,cohort studies or inception cohorts provided data that the long term disease course is better,when mucosal healing is achieved.However,it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission.Clinical trials are under way to answer this question.Attention should be paid to clearly address what levels of IBD activity are looked at.In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists. | Gerhard Rogler Stephan Vavricka Alain Schoepfer Peter L Lakatos | 2013 | World Journal of Gastroenterology2013，19，43： | 4 |
| 9 | Protein tyrosine phosphatase non-receptor type 2 andinflammatory bowel disease显示文摘Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2(PTPN2) with the onset of inflammatory bowel disease(IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation. | Marianne R Spalinger Declan F McCole Gerhard Rogler Michael Scharl | 2016 | World Journal of Gastroenterology2016，22，3： | 4 |
| 10 | Second European evidence-based consensus on the diagnosis and management of ulcerative colitis: Special situations显示文摘 | Gert Van Assche Axel Dignass Bernd Bokemeyer Silvio Danese Paolo Gionchetti Gabriele Moser Laurent Beaugerie Fernando Gomollón Winfried H?user Klaus Herrlinger Bas Oldenburg Julian Panes Francisco Portela Gerhard Rogler Jürgen Stein Herbert Tilg Simon Tra | 2012 | Journal of Crohn’s and Colitis2012，，： | 4 |
| 11 | Role of soluble factors and three-dimensional culture in in vitro differentiation of intestinal macrophages显示文摘AIM: To examine the factor(s) involved in differentiation of intestinal macrophages (IMACs) using a recently established in vitro model. METHODS: To test whether soluble or membrane bound factors induce IMAC-differentiation, freshly elutriated monocytes (MO) were incubated with conditioned media or cell membranes of intestinal epithelial cells (IEC) or cultured with IEC in transwell systems. To determine the importance of an active migration of MO, three- dimensional aggregates from a 1:1-mixture of MO and IEC were examined by immunohistochemistry and flow cytometry. Apoptosis was examined by caspase-3 Western blots. Extracellular matrix production in differentiation models was compared by immunohistochemistry. RESULTS: IMAC differentiation was observed in a complex three-dimensional co-culture model (multicellular spheroid, MCS) with IEC after migration of MO into the spheroids. By co-culture of MO with conditioned media or membrane preparations of IEC no IMAC differentiation was induced. Co-culture of MO with IEC in transwell- cultures, with the two cell populations separated by a membrane also did not result in intestinal-like differentiation of MO. In contrast to IEC-spheroids with immigrating MO in mixed MCS of IEC and MO only a small subpopulation of MO was able to survive the seven day culture period. CONCLUSION: Intestinal-like differentiation of MO in vitro is only induced in the complex three-dimensional MCS model after immigration of MO indicating a roleof cell-matrix and/or cell-cell interactions during the differentiation of IMACs. | Tanja Spoettl Martin Hausmann Katrin Menzel Heidi Piberger Hans Herfarth Juergen Schoelmerich Frauke Bataille Gerhard Rogler | 2007 | World Journal of Gastroenterology2007，13，7： | 3 |
| 12 | The incidence of inflammatory bowel disease in a rural region of Southern Germany: a prospective population-based study显示文摘 | Claudia Ott Florian Obermeier Sabine Thieler Daniela Kemptner Alexandra Bauer Jürgen Sch?lmerich Gerhard Rogler Antje Timmer | 2008 | European Journal of Gastroenterology & Hepatology2008，，9： | 1 |
| 13 | The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Definitions and diagnosis显示文摘 | Gert Van Assche Axel Dignass Julian Panes Laurent Beaugerie John Karagiannis Mathieu Allez Thomas Ochsenkühn Tim Orchard Gerhard Rogler Edouard Louis Limas Kupcinskas Gerassimos Mantzaris Simon Travis Eduard Stange | 2009 | Journal of Crohn’s and Colitis2009，，1： | 1 |
| 14 | Activated transcription Factor Nuclear factor kappa B is present in the Atherosclerotic lesion显示文摘 | Korbinian Brand Sharon Page Gerhard Rogler | 1996 | J Clin lnvest1996，97，7： | 1 |
| 15 | Chronic ulcerative colitis and colorectal cancer显示文摘 | Gerhard Rogler | 2014 | Cancer Letters2014，，2： | 1 |
| 16 | Prior bowel resections, perianal disease, and a high initial Crohn’s disease activity index are associated with corticosteroid resistance in active Crohn’s disease显示文摘 | Cornelia M Gelbmann Gerhard Rogler Volker Gross Michael Gierend Nicole Bregenzer Tilo Andus Jürgen Sch?lmerich | 2002 | The American Journal of Gastroenterology2002，，6： | 1 |
| 17 | Extraintestinal Manifestations of Inflammatory Bowel Disease显示文摘 | Stephan R. Vavricka Alain Schoepfer Michael Scharl Peter L. Lakatos Alexander Navarini Gerhard Rogler | 2015 | Inflammatory Bowel Diseases2015，，8： | 1 |
| 18 | Comparison of capsule endoscopy and magnetic resonance (MR) enteroclysis in suspected small bowel disease显示文摘 | Stefan K. G?lder Andreas G. Schreyer Esther Endlicher Stefan Feuerbach Jürgen Sch?lmerich Frank Kullmann Johannes Seitz Gerhard Rogler Hans Herfarth | 2006 | International Journal of Colorectal Disease2006，，2： | 1 |
| 19 | Su1261 Expression of Interleukins 22 and 33, Matrix Metalloproteinases 9 and 13, Mast Cell Markers and Hypoxia-Inducible Factor 1α in Crohn’s Disease Associated Fistulae显示文摘 | Sandra M. Frei Silvia Lang Ekkehard C. Jehle Michael Fried Gerhard Rogler Michael Scharl | 2013 | Gastroenterology2013，，5： | 1 |
| 20 | Periodontitis and Gingivitis in Inflammatory Bowel Disease: A Case–Control Study显示文摘 | Stephan R. Vavricka Christine N. Manser Sebastian Hediger Marius V?gelin Michael Scharl Luc Biedermann Sebastian Rogler Frank Seibold René Sanderink Thomas Attin Alain Schoepfer Michael Fried Gerhard Rogler Pascal Frei | 2013 | Inflammatory Bowel Diseases2013，，13： | 1 |
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