Results of the 2nd scientific workshop of the ECCO (III): basic mechanisms of intestinal healing.

The second scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal healing for the disease course of inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms, markers for disease prediction, detection and monitoring of intestinal healing, impact of intestinal healing on the disease course of IBD as well as therapeutic strategies. The results of this workshop are presented in four separate manuscripts. This section describes basic mechanisms of intestinal healing, identifies open questions in the field and provides a framework for future studies.

[1]  L. Pellegrinet.  The Intestinal Epithelium , 2011 .

[2]  C. Jobin,et al.  PI3K-Dependent GSK3ß(Ser9)-Phosphorylation Is Implicated in the Intestinal Epithelial Cell Wound-Healing Response , 2011, PloS one.

[3]  D. Granger,et al.  Regulation of Murine Intestinal Inflammation by Reactive Metabolites of Oxygen and Nitrogen , 2001, The Journal of experimental medicine.

[4]  F. Rieux-Laucat,et al.  Induction of T lymphocyte apoptosis by sulphasalazine in patients with Crohn’s disease , 2004, Gut.

[5]  S. Colgan,et al.  Mucosal protection by hypoxia‐inducible factor (HIF) prolyl hydroxylase inhibition , 2008 .

[6]  C. Jobin,et al.  Gnotobiotic IL-10−/−;NF-κBEGFP Mice Reveal the Critical Role of TLR/NF-κB Signaling in Commensal Bacteria-Induced Colitis1 , 2007, The Journal of Immunology.

[7]  G. Rogler,et al.  Sphingomyelin induces cathepsin D-mediated apoptosis in intestinal epithelial cells and increases inflammation in DSS colitis , 2010, Gut.

[8]  J. Ioannidis,et al.  Differential Effects of NOD2 Variants on Crohn's Disease Risk and Phenotype in Diverse Populations: A Metaanalysis , 2004, The American Journal of Gastroenterology.

[9]  P. Kubes,et al.  Role of inducible nitric oxide synthase in trinitrobenzene sulphonic acid induced colitis in mice , 1999, Gut.

[10]  G. Besner,et al.  HB-EGF enhances restitution after intestinal ischemia/reperfusion via PI3K/Akt and MEK/ERK1/2 activation. , 2005, Gastroenterology.

[11]  O. Inatomi,et al.  Butyrate blocks interferon-γ-inducible protein-10 release in human intestinal subepithelial myofibroblasts , 2005, Journal of Gastroenterology.

[12]  J. Wehkamp,et al.  Barrier dysfunction due to distinct defensin deficiencies in small intestinal and colonic Crohn's disease , 2008, Mucosal Immunology.

[13]  D. Podolsky,et al.  Transforming growth factor β regulation of migration in wounded rat intestinal epithelial monolayers , 1993 .

[14]  M. Peppelenbosch,et al.  Dichotomal role of inhibition of p38 MAPK with SB 203580 in experimental colitis , 2002, Gut.

[15]  B. Wiedenmann,et al.  Escherichia coli Strain Nissle 1917 Ameliorates Experimental Colitis via Toll-Like Receptor 2- and Toll-Like Receptor 4-Dependent Pathways , 2006, Infection and Immunity.

[16]  R. Sartor.  Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis , 2006, Nature Clinical Practice Gastroenterology &Hepatology.

[17]  P. Gibson,et al.  Short-chain fatty acids promote the migration of colonic epithelial cells in vitro. , 1997, Gastroenterology.

[18]  M. Neurath,et al.  Epithelial NEMO links innate immunity to chronic intestinal inflammation , 2007, Nature.

[19]  T. Klaenhammer,et al.  Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[20]  B. Zingarelli,et al.  Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase , 1999, Gut.

[21]  Tariq Ahmad,et al.  Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47 , 2011, Nature Genetics.

[22]  S. Targan,et al.  A soluble factor produced by lamina propria mononuclear cells is required for TNF-alpha enhancement of IFN-gamma production by T cells. , 1999, Journal of immunology.

[23]  F Verrecchia,et al.  [Cellular and molecular mechanisms of fibrosis]. , 2006, Annales de pathologie.

[24]  T. Menzel,et al.  Butyrate Inhibits Interleukin-1-Mediated Nuclear Factor-Kappa B Activation in Human Epithelial Cells , 2001, Digestive Diseases and Sciences.

[25]  Fabio Cominelli,et al.  Probiotics promote gut health through stimulation of epithelial innate immunity , 2009, Proceedings of the National Academy of Sciences.

[26]  M. Fishman,et al.  Impaired Defense of Intestinal Mucosa in Mice Lacking Intestinal Trefoil Factor , 1996, Science.

[27]  M. Sans,et al.  Effects of steroid treatment on activation of nuclear factor κB in patients with inflammatory bowel disease , 1998, British journal of pharmacology.

[28]  G. Rogler,et al.  Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo , 2006, Clinical and experimental immunology.

[29]  M. Baker,et al.  Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. , 1996, The Journal of clinical investigation.

[30]  Jerrold R. Turner,et al.  Intestinal mucosal barrier function in health and disease , 2009, Nature Reviews Immunology.

[31]  A. Dignass,et al.  Epithelial restitution and wound healing in inflammatory bowel disease. , 2008, World journal of gastroenterology.

[32]  M. Washington,et al.  Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. , 2007, Gastroenterology.

[33]  J. Belaiche,et al.  Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease , 2001, Gut.

[34]  J. Westwick,et al.  Expression of inducible nitric oxide synthase activity in human colon epithelial cells: modulation by T lymphocyte derived cytokines , 1998, Gut.

[35]  P. Rutgeerts,et al.  Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab† , 2010, Inflammatory bowel diseases.

[36]  A. Gasbarrini,et al.  TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn's disease. , 2006, Journal of immunology.

[37]  G. Hansson,et al.  A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn. , 2009, Glycobiology.

[38]  H. Verspaget,et al.  Differential mucosal expression of three superoxide dismutase isoforms in inflammatory bowel disease , 2003, The Journal of pathology.

[39]  M. Frey,et al.  Epidermal Growth Factor-stimulated Intestinal Epithelial Cell Migration Requires Src Family Kinase-dependent p38 MAPK Signaling* , 2004, Journal of Biological Chemistry.

[40]  M. Kleerebezem,et al.  Improvement of an experimental colitis in rats by lactic acid bacteria producing superoxide dismutase , 2006, Inflammatory Bowel Diseases.

[41]  J. Galmiche,et al.  Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. , 2000, Gut.

[42]  H. Tilg,et al.  XBP1 Links ER Stress to Intestinal Inflammation and Confers Genetic Risk for Human Inflammatory Bowel Disease , 2008, Cell.

[43]  S. Rosewicz,et al.  Di V erential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease , 2000 .

[44]  J. Söderholm,et al.  Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate† , 2010, Inflammatory bowel diseases.

[45]  H. Blottière,et al.  Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. , 2004, American journal of physiology. Gastrointestinal and liver physiology.

[46]  R. Xavier,et al.  Unravelling the pathogenesis of inflammatory bowel disease , 2007, Nature.

[47]  P. Janmey,et al.  Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[48]  M. Manns,et al.  Effects of azathioprine and its metabolites on repair mechanisms of the intestinal epithelium in vitro , 2005, Regulatory Peptides.

[49]  W. Stremmel,et al.  Phosphatidylcholine as a constituent in the colonic mucosal barrier--physiological and clinical relevance. , 2010, Biochimica et biophysica acta.

[50]  M. Schwab,et al.  Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells. , 2007, Molecular immunology.

[51]  M. Dwinell,et al.  CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells* , 2009, Journal of Biological Chemistry.

[52]  M. Weichenthal,et al.  Reduced Paneth cell alpha-defensins in ileal Crohn's disease. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[53]  A. Mobasheri,et al.  Targeting matrix metalloproteinases in inflammatory conditions. , 2009, Current drug targets.

[54]  W. Tong,et al.  Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis , 2008, Proceedings of the National Academy of Sciences.

[55]  A. Dignass.  Mechanisms and modulation of intestinal epithelial repair. , 2001, Inflammatory bowel diseases.

[56]  M. Spehlmann,et al.  Nuclear factor-kappa B in intestinal protection and destruction , 2009, Current opinion in gastroenterology.

[57]  G. Rogler,et al.  Diagnosis and management of fistulizing Crohn's disease , 2009, Nature Clinical Practice Gastroenterology &Hepatology.

[58]  Markus F Neurath,et al.  Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. , 2007, Gastroenterology.

[59]  S. Czinn,et al.  Bacterial Probiotic Modulation of Dendritic Cells , 2004, Infection and Immunity.

[60]  G. Corazza,et al.  Stromelysin-1 and macrophage metalloelastase expression in the intestinal mucosa of Crohn's disease patients treated with infliximab , 2009, European journal of gastroenterology & hepatology.

[61]  B. Bass,et al.  Bile salt stimulates intestinal epithelial cell migration through TGFbeta after wounding. , 2001, The Journal of surgical research.

[62]  A. Dignass,et al.  Corticosteroids impair intestinal epithelial wound repair mechanisms in vitro. , 2000, Scandinavian journal of gastroenterology.

[63]  Isabelle Cleynen,et al.  Mucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment , 2009, PloS one.

[64]  R. Odze,et al.  Effect of topical 5-aminosalicylic acid (5-ASA) therapy on rectal mucosal biopsy morphology in chronic ulcerative colitis. , 1993, The American journal of surgical pathology.

[65]  C. Pothoulakis,et al.  The angiogenic effect of probiotic Bacillus polyfermenticus on human intestinal microvascular endothelial cells is mediated by IL-8. , 2009, American journal of physiology. Gastrointestinal and liver physiology.

[66]  M. Frey,et al.  The ErbB4 growth factor receptor is required for colon epithelial cell survival in the presence of TNF. , 2009, Gastroenterology.

[67]  H. Lochs,et al.  Azathioprine and mesalazine‐induced effects on the mucosal flora in patients with IBD colitis , 2007, Inflammatory bowel diseases.

[68]  T. Nishimura,et al.  Inhibitory Effects of Short-Chain Fatty Acids on Matrix Metalloproteinase Secretion from Human Colonic Subepithelial Myofibroblasts , 2009, Digestive Diseases and Sciences.

[69]  K. Kato,et al.  Effects of growth factors and trefoil peptides on migration and replication in primary oxyntic cultures , 1999 .

[70]  O. Lider,et al.  Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation , 2000, Journal of leukocyte biology.

[71]  I. Finnie,et al.  Colonic mucin synthesis is increased by sodium butyrate. , 1995, Gut.

[72]  M. Manns,et al.  Differential glucocorticoid effects on repair mechanisms and NF-κB activity in the intestinal epithelium , 2002, Regulatory Peptides.

[73]  Y. Matsuzawa,et al.  Role of prostaglandins in intestinal epithelial restitution stimulated by growth factors. , 1996, The American journal of physiology.

[74]  Matthias Chiquet,et al.  From mechanotransduction to extracellular matrix gene expression in fibroblasts. , 2009, Biochimica et biophysica acta.

[75]  Lena Holm,et al.  The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria , 2010, Gut microbes.

[76]  J. Stachura,et al.  Vascular and Microvascular Changes—Key Factors in the Development of Acetic Acid‐Induced Gastric Ulcers in Rats , 1990, Journal of clinical gastroenterology.

[77]  C. Hawkey,et al.  5-Aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease. , 1991, Gut.

[78]  K. Morimura,et al.  Hypoxia-inducible factor augments experimental colitis through an MIF-dependent inflammatory signaling cascade. , 2008, Gastroenterology.

[79]  P. Rutgeerts,et al.  Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn's disease , 2005, Current medical research and opinion.

[80]  B. Wiedenmann,et al.  Mesalamine promotes intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism , 2005, Scandinavian journal of gastroenterology.

[81]  M. Karin,et al.  The two faces of IKK and NF-κB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion , 2003, Nature Medicine.

[82]  N. Docherty,et al.  Fibrogenesis in Crohn's Disease , 2007, The American Journal of Gastroenterology.

[83]  Johannes Buchner,et al.  Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1 , 2011, Nature.

[84]  M. Vieth,et al.  Mesalazine inhibits activation of transcription factor NF-κB in inflamed mucosa of patients with ulcerative colitis , 2000, American Journal of Gastroenterology.

[85]  John E Tomaszewski,et al.  Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. , 2004, The Journal of clinical investigation.

[86]  P. Rutgeerts,et al.  Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. , 1999, Gastroenterology.

[87]  T. Macdonald,et al.  Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells. , 2000, American journal of physiology. Gastrointestinal and liver physiology.

[88]  P. Rutgeerts,et al.  Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease , 2002, American Journal of Gastroenterology.

[89]  S. Ng,et al.  Mechanisms of action of probiotics: Recent advances , 2009, Inflammatory bowel diseases.

[90]  K. Kaltoft,et al.  Infliximab downregulates interferon-gamma production in activated gut T-lymphocytes from patients with Crohn's disease. , 2001, Cytokine.

[91]  W. Walker,et al.  Butyrate Regulates the Expression of Pathogen-Triggered IL-8 in Intestinal Epithelia , 2007, Pediatric Research.

[92]  D. Sachar.  Behaviour of Crohn's disease according to the Vienna classification , 2002, Gut.

[93]  S. Hogan,et al.  Intestinal barrier function: molecular regulation and disease pathogenesis. , 2009, The Journal of allergy and clinical immunology.

[94]  T. Macdonald,et al.  Tumor necrosis factor α-producing cells in the intestinal mucosa of children with inflammatory bowel disease , 1994 .

[95]  M. Tretiakova,et al.  Distinct temporal-spatial roles for rho kinase and myosin light chain kinase in epithelial purse-string wound closure. , 2005, Gastroenterology.

[96]  E. Remaut,et al.  Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. , 2004, Gastroenterology.

[97]  A. Lacy,et al.  Crohn's Disease Patients Carrying Nod2/CARD15 Gene Variants Have an Increased and Early Need for First Surgery due to Stricturing Disease and Higher Rate of Surgical Recurrence , 2005, Annals of surgery.

[98]  Sarah L. Brown,et al.  Efficient colonic mucosal wound repair requires Trem2 signaling , 2009, Proceedings of the National Academy of Sciences.

[99]  D. Foell,et al.  Mechanisms of Disease: a 'DAMP' view of inflammatory arthritis , 2007, Nature Clinical Practice Rheumatology.

[100]  J. Bouma,et al.  Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: mucin 2-interleukin 10-deficient mice , 2008, Laboratory Investigation.

[101]  M. Chamaillard,et al.  Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon , 2010, Proceedings of the National Academy of Sciences.

[102]  Wei Wang,et al.  Protective effect of ilomastat on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats. , 2008, World journal of gastroenterology.

[103]  T. Ziegler,et al.  Colonic leptin: source of a novel pro‐inflammatory cytokine involved in inflammatory bowel disease , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[104]  H. Flint,et al.  The microbiology of butyrate formation in the human colon. , 2002, FEMS microbiology letters.

[105]  C. Jobin,et al.  Gnotobiotic IL-10-/-;NF-kappa B(EGFP) mice reveal the critical role of TLR/NF-kappa B signaling in commensal bacteria-induced colitis. , 2007, Journal of immunology.

[106]  G. Rogler,et al.  Wound healing and fibrosis in intestinal disease , 2006, Gut.

[107]  S. Lightfoot,et al.  Luminal Antioxidants Enhance the Effects of Mesalamine in the Treatment of Chemically Induced Colitis in Rats , 2008, Experimental biology and medicine.

[108]  Tariq Ahmad,et al.  Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci , 2010, Nature Genetics.

[109]  S. Targan,et al.  Bacterial flagellin is a dominant antigen in Crohn disease. , 2004, The Journal of clinical investigation.

[110]  W. Stremmel,et al.  Delayed release phosphatidylcholine as new therapeutic drug for ulcerative colitis – a review of three clinical trials , 2010, Expert opinion on investigational drugs.

[111]  W. Lehmann,et al.  Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: A clue to pathogenesis , 2009, Inflammatory bowel diseases.

[112]  K. Okita,et al.  Increased expression of tumor necrosis factor-α messenger RNA in the intestinal mucosa of inflammatory bowel disease, particularly in patients with disease in the inactive phase , 2002, Journal of Gastroenterology.

[113]  H. Verspaget,et al.  Increased mucosal matrix metalloproteinase-1, -2, -3 and -9 activity in patients with inflammatory bowel disease and the relation with Crohn's disease phenotype. , 2007, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[114]  Ruslan Medzhitov,et al.  Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis , 2004, Cell.

[115]  C. A. de la Motte,et al.  Inflammation-induced endothelial-to-mesenchymal transition: a novel mechanism of intestinal fibrosis. , 2011, The American journal of pathology.

[116]  A. Morelli,et al.  Inhibition of Intestinal Bacterial Translocation with Rifaximin Modulates Lamina propria Monocytic Cells Reactivity and Protects against Inflammation in a Rodent Model of Colitis , 2003, Digestion.

[117]  G Van Assche,et al.  Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis , 2009, Gut.

[118]  C. Pothoulakis,et al.  Metalloproteinases and Transforming Growth Factor-α Mediate Substance P-induced Mitogen-activated Protein Kinase Activation and Proliferation in Human Colonocytes* , 2004, Journal of Biological Chemistry.

[119]  B. Pulendran,et al.  Activation of β-Catenin in Dendritic Cells Regulates Immunity Versus Tolerance in the Intestine , 2010, Science.

[120]  M. Weichenthal,et al.  Reduced Paneth cell α-defensins in ileal Crohn's disease , 2005 .

[121]  D. Podolsky,et al.  Hepatocyte growth factor/scatter factor modulates intestinal epithelial cell proliferation and migration. , 1994, Biochemical and biophysical research communications.

[122]  A. Baldwin,et al.  Wound‐induced p38MAPK‐dependent histone H3 phosphorylation correlates with increased COX‐2 expression in enterocytes , 2006, Journal of cellular physiology.

[123]  S. Brand,et al.  Human beta defensin 2 promotes intestinal wound healing in vitro , 2008, Journal of cellular biochemistry.

[124]  P. Rutgeerts,et al.  Endoscopic and histologic healing of Crohn's (ileo-) colitis with azathioprine. , 1999, Gastrointestinal endoscopy.

[125]  Linheng Li,et al.  Interferon-gamma regulates intestinal epithelial homeostasis through converging beta-catenin signaling pathways. , 2010, Immunity.

[126]  G. Kolios,et al.  Ciprofloxacin inhibits cytokine‐induced nitric oxide production in human colonic epithelium , 2006, European journal of clinical investigation.

[127]  Fiona Campbell,et al.  Characterization of epithelial cell shedding from human small intestine , 2006, Laboratory Investigation.

[128]  Ian R. Holzman,et al.  Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. , 2009, The Journal of nutrition.

[129]  S. Akira,et al.  Enterocyte-Derived TAK1 Signaling Prevents Epithelium Apoptosis and the Development of Ileitis and Colitis1 , 2008, The Journal of Immunology.

[130]  S. Hanks,et al.  Regulation of FAK Ser-722 phosphorylation and kinase activity by GSK3 and PP1 during cell spreading and migration. , 2005, The Biochemical journal.

[131]  Jason M Doherty,et al.  Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[132]  C. Jobin,et al.  Wound healing responses at the gastrointestinal epithelium: a close look at novel regulatory factors and investigative approaches. , 2009, Zeitschrift fur Gastroenterologie.

[133]  C. Jobin,et al.  NF‐&kgr;B and the intestine: Friend or foe? , 2008 .

[134]  A. Watson,et al.  Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. , 2005, Gastroenterology.

[135]  D. Bernardo,et al.  High Levels of Proinflammatory Cytokines, but Not Markers of Tissue Injury, in Unaffected Intestinal Areas from Patients with IBD , 2009, Mediators of inflammation.

[136]  M. Kagnoff,et al.  Nuclear factor-κB activation promotes restitution of wounded intestinal epithelial monolayers , 2003 .

[137]  T. Macdonald,et al.  Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. , 1994, Gastroenterology.

[138]  M. Basson,et al.  Smad3 knockout mice exhibit impaired intestinal mucosal healing , 2008, Laboratory Investigation.

[139]  O. Fratila,et al.  Ultrastructural evidence of mucosal healing after infliximab in patients with ulcerative colitis. , 2010, Journal of gastrointestinal and liver diseases : JGLD.

[140]  C. Fiocchi,et al.  Intestinal fibrosis in IBD—a dynamic, multifactorial process , 2009, Nature Reviews Gastroenterology &Hepatology.