Genome-wide expression profiling implicates a MAST3-regulated gene set in colonic mucosal inflammation of ulcerative colitis patients.

Abstract:

BACKGROUND:Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) presumably caused by dysregulated immune responses to the gut microbiota. Genetic association studies have implicated dozens of chromosomal regions or loci in IBD susceptibility. The next challenge is to explain the individual role of each of these modest effect loci in the disease state. We have previously identified MAST3 as an IBD susceptibility gene through genetic fine-mapping of the 19p linkage region. Testing MAST3 in a reporter assay provided preliminary evidence that MAST3 modulates the activity of inflammation-related transcription factor nuclear factor kappa B. METHODS:Here we characterized the function of MAST3 through an examination of the influence of the modulation of MAST3 expression on endogenous genome-wide expression patterns. More specifically, we looked at differential gene expression resulting from overexpression and knockdown of the MAST3 gene in epithelial and macrophage cell lines. From we highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-jB activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD. RESULTS:We highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-κB activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD. These MAST3-regulated genes are central to mucosal immune responses. Among them are proinflammatory cytokines (e.g., CCL20, IL8), regulators of NF-κB (e.g., TNFAIP3, LY96, NFKBIA), genes involved in interferon-induced defense against pathogen invasion (e.g., IFIT1, ISG15), and genes involved in cell adhesion and/or migration (e.g., CD44, TMOD1). CONCLUSIONS:Taken together, these results confirm MAST3 as a modulator of the inflammatory response through regulation of immune gene expression in the gut of IBD patients.

journal_name

Inflamm Bowel Dis

authors

Labbé C,Boucher G,Foisy S,Alikashani A,Nkwimi H,David G,Beaudoin M,Goyette P,Charron G,Xavier RJ,Rioux JD

doi

10.1002/ibd.21887

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

1072-80

issue

6

eissn

1078-0998

issn

1536-4844

journal_volume

18

pub_type

杂志文章
  • Diagnostic Accuracy of Blood-Based Tests and Histopathology for Cytomegalovirus Reactivation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

    abstract:BACKGROUND:It is unclear if traditional histopathology and noninvasive blood-based tests are sufficiently accurate to detect cytomegalovirus (CMV) reactivation in inflammatory bowel disease. Therefore, we assessed the diagnostic accuracy of these tests compared with immunohistochemistry (IHC) and tissue polymerase chai...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析,评审

    doi:10.1097/MIB.0000000000001073

    authors: Tandon P,James P,Cordeiro E,Mallick R,Shukla T,McCurdy JD

    更新日期:2017-04-01 00:00:00

  • The case for using 5-aminosalicyclates in Crohn's disease: pro.

    abstract::Mesalamine has a well-established role in the management of ulcerative colitis. However, its role in the management of Crohn's disease (CD) is less clear. Studies evaluating its therapeutic value in CD have produced both positive and negative results. Meta-analyses have not clarified the situation, possibly because th...

    journal_title:Inflammatory bowel diseases

    pub_type: 评论,社论

    doi:10.1097/01.mib.0000160743.24772.69

    authors: Hanauer SB

    更新日期:2005-06-01 00:00:00

  • Immunoregulatory Pathways Involved in Inflammatory Bowel Disease.

    abstract::Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn's disease. The immune response in ulcerative colitis is different from the Crohn's disease. Accumulating evidence suggests that IBD results from an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host. Severa...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1097/MIB.0000000000000477

    authors: Fonseca-Camarillo G,Yamamoto-Furusho JK

    更新日期:2015-09-01 00:00:00

  • Impact of timing and duration of thiopurine treatment on first perianal surgery in Crohn's disease: UK population-based study (1995-2009).

    abstract:BACKGROUND:The impact of thiopurine (TP) use on perianal surgery is uncertain. Our aim was to determine trends in perianal surgery and the impact of timing and duration of TPs on the risk of first perianal surgery. METHODS:We identified a population-based cohort of incident cases of Crohn's disease between 1995 and 20...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000290

    authors: Chhaya V,Saxena S,Cecil E,Subramanian V,Curcin V,Majeed A,Pollok RC

    更新日期:2015-02-01 00:00:00

  • Etiology of pouchitis.

    abstract::Restorative proctocolectomy with ileal-pouch anal anastomosis (RPC) is the operation of choice for ulcerative colitis (UC) patients requiring surgery. It is also used for patients with familial adenomatous polyposis (FAP). Pouchitis accounts for 10% of pouch failures. It is an idiopathic inflammatory condition that ma...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.21911

    authors: Landy J,Al-Hassi HO,McLaughlin SD,Knight SC,Ciclitira PJ,Nicholls RJ,Clark SK,Hart AL

    更新日期:2012-06-01 00:00:00

  • Mucosal healing in Crohn's disease: a systematic review.

    abstract::The traditional goals of Crohn's disease therapy, to induce and maintain clinical remission, have not clearly changed its natural history. In contrast, emerging evidence suggests that achieving and maintaining mucosal healing may alter the natural history of Crohn's disease, as it has been associated with more sustain...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.22977

    authors: De Cruz P,Kamm MA,Prideaux L,Allen PB,Moore G

    更新日期:2013-02-01 00:00:00

  • Comparative Evaluation of Conventional Stool Testing and Multiplex Molecular Panel in Outpatients With Relapse of Inflammatory Bowel Disease.

    abstract:BACKGROUND:Differentiating between enteric infection and relapse of inflammatory bowel disease (IBD) is a common clinical challenge. Few studies have evaluated the impact of multiplex gastrointestinal polymerase chain reaction (GI PCR) pathogen panels on clinical practice compared to stool culture. Our aim was to compa...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa336

    authors: Hong S,Zaki TA,Main M,Hine AM,Chang S,Hudesman D,Axelrad JE

    更新日期:2021-01-02 00:00:00

  • Immunoregulatory Role of Myeloid-derived Cells in Inflammatory Bowel Disease.

    abstract::As the frontiers of immunological research expand, new insights into the pathogenesis of long poorly understood diseases, such as inflammatory bowel disease (IBD), are opening up new possible avenues for treatment. Myeloid-derived cells (i.e., monocytes, macrophages, neutrophils, and dendritic cells), long believed to...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000511

    authors: Leal MC,Däbritz J

    更新日期:2015-12-01 00:00:00

  • Low Indeterminate Rates Associated With Use of the QuantiFERON-TB Gold In-Tube Test in Children With Inflammatory Bowel Disease on Long-term Infliximab.

    abstract:Background:Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term tr...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izx077

    authors: Vortia E,Uko VE,Yen-Lieberman B,Frawley J,Worley SE,Danziger-Isakov L,Kaplan B,Mahajan L

    更新日期:2018-03-19 00:00:00

  • Outcomes of Perianal Fistulising Crohn's Disease Following Anti-TNFα Treatment Discontinuation.

    abstract:Background:Discontinuation of antitumour necrosis factor (TNF)α therapy with perianal fistulising Crohn's disease remains controversial due to the risk of severe relapse without any clear evidence. Aim:The aim of this study was to assess the rate and type of perianal and luminal relapses following anti-TNFα discontinu...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy008

    authors: Legué C,Brochard C,Bessi G,Wallenhorst T,Dewitte M,Siproudhis L,Bouguen G

    更新日期:2018-05-18 00:00:00

  • Clinically Significant Small Bowel Crohn's Disease Might Only be Detected by Capsule Endoscopy.

    abstract:Background:In Crohn's disease (CD) a small bowel study-in addition to colonoscopy-is considered necessary for diagnosis/staging. In this study we re-examined the role of capsule endoscopy (CE), colonoscopy, imaging tests [magnetic resonance enterography/computed tomographic enterography (MRE/CTE)], and inflammatory mar...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy048

    authors: Sorrentino D,Nguyen VQ

    更新日期:2018-06-08 00:00:00

  • Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

    abstract:Background:Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods:In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy166

    authors: Lauritzen D,Andreassen BU,Heegaard NHH,Klinge LG,Walsted AM,Neland M,Nielsen RG,Wittenhagen P

    更新日期:2018-11-29 00:00:00

  • Implications of the colonic deposition of free hemoglobin-α chain: a previously unknown tissue by-product in inflammatory bowel disease.

    abstract:BACKGROUND:We analyzed inflamed mucosal/submucosal layers of ulcerative colitis (UC = 63) and Crohn's colitis (CC = 50), and unexpectedly, we unveiled a pool of free hemoglobin alpha (Hb-α) chain. Patients with colitides have increased reactive oxidative stress (ROS), DNA oxidation products, free iron in mucosa, in pre...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000144

    authors: Myers JN,Schäffer MW,Korolkova OY,Williams AD,Gangula PR,MʼKoma AE

    更新日期:2014-09-01 00:00:00

  • Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.

    abstract:BACKGROUND:A notable proportion of patients with inflammatory bowel disease (IBD) are switched from infliximab (IFX) to adalimumab (ADL). We investigated if immunogenicity of IFX influenced immunogenicity and clinical outcomes of later ADL therapy. METHODS:Single-center cohort study including all patients with IBD ass...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章

    doi:10.1097/MIB.0000000000000138

    authors: Frederiksen MT,Ainsworth MA,Brynskov J,Thomsen OO,Bendtzen K,Steenholdt C

    更新日期:2014-10-01 00:00:00

  • Impact of prior irregular infliximab dosing on performance of long-term infliximab maintenance therapy in Crohn's disease.

    abstract:BACKGROUND:Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. METHODS:This was a retrospective, observational study of CD pat...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21164

    authors: Stein DJ,Ananthakrishnan AN,Issa M,Williams JB,Beaulieu DB,Zadvornova Y,Ward A,Johnson K,Knox JF,Skaros S,Binion DG

    更新日期:2010-07-01 00:00:00

  • Correlation of Stool Frequency and Abdominal Pain Measures With Simple Endoscopic Score for Crohn's Disease.

    abstract:BACKGROUND:The Crohn's Disease Activity Index (CDAI) has been criticized for being weakly correlated with bowel inflammation. We assessed correlation between Simple Endoscopic Score for Crohn's Disease (SES-CD) and individual CDAI items stratified by disease location to better understand this relationship. METHODS:We ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izz241

    authors: Lewis JD,Rutgeerts P,Feagan BG,D'haens G,Danese S,Colombel JF,Reinisch W,Rubin DT,Selinger C,Bewtra M,Barcomb L,Lacerda AP,Wallace K,Butler JW,Wu M,Zhou Q,Liao X,Sandborn WJ

    更新日期:2020-01-06 00:00:00

  • Dilation of colonic strictures by intralesional injection of infliximab in patients with Crohn's colitis.

    abstract:BACKGROUND:Intestinal stenosis is a frequent complication of Crohn's disease, often leading to repeated bowel obstruction and surgery. The prevalence of small bowel stenosis has ranged from 20% to 40% and from 7% to 15% in patients with colonic disease. Although balloon dilation is the initial preferred approach, many ...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章,评审

    doi:10.1002/ibd.20318

    authors: Swaminath A,Lichtiger S

    更新日期:2008-02-01 00:00:00

  • Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease.

    abstract:BACKGROUND:The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. METHODS:A total of 158 twins with ulcerative ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20242

    authors: Halfvarson J,Jess T,Bodin L,Järnerot G,Munkholm P,Binder V,Tysk C

    更新日期:2007-12-01 00:00:00

  • A Population Pharmacokinetic and Exposure-Response Model of Golimumab for Targeting Endoscopic Remission in Patients With Ulcerative Colitis.

    abstract:BACKGROUND:Unlike other anti-tumor necrosis factor alpha antibodies, golimumab does not deliver on its promise of effectiveness for treating patients with ulcerative colitis. We investigated the value of therapeutic drug monitoring for optimizing golimumab therapy. METHODS:We analyzed the golimumab pharmacokinetics da...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izz144

    authors: Dreesen E,Kantasiripitak W,Detrez I,Stefanović S,Vermeire S,Ferrante M,Bouillon T,Drobne D,Gils A

    更新日期:2020-03-04 00:00:00

  • TNFRSF1B Is Associated with ANCA in IBD.

    abstract::The genetic basis of antineutrophil cytoplasmic antibody, an important biomarker of inflammatory bowel disease (IBD), has never been thoroughly examined on a genome-wide scale. In this study, we performed a 2-stage genome-wide association study (GWAS) on antineutrophil cytoplasmic antibody in IBD cases. In the 2959 IB...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析

    doi:10.1097/MIB.0000000000000771

    authors: Li D,Silverberg MS,Haritunians T,Dubinsky MC,Landers C,Stempak JM,Milgrom R,Guo X,Chen YD,Rotter JI,Taylor KD,McGovern DP,Targan SR

    更新日期:2016-06-01 00:00:00

  • Inflammatory bowel disease in Chinese children: a multicenter analysis over a decade from Shanghai.

    abstract:BACKGROUND:The purpose was to estimate the incidence and characteristics of childhood inflammatory bowel disease (IBD) during 2000-2010 in Shanghai, China. METHODS:IBD patients between the ages of 0 and 18 years old were identified by survey of computerized medical information. Relevant data were extracted from their ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1097/MIB.0b013e318286f9f2

    authors: Wang XQ,Zhang Y,Xu CD,Jiang LR,Huang Y,Du HM,Wang XJ

    更新日期:2013-02-01 00:00:00

  • Clostridium difficile Infection and Risk of Colectomy in Patients with Inflammatory Bowel Disease: A Bias-adjusted Meta-analysis.

    abstract:BACKGROUND:Clostridium difficile infection (CDI) is a common complication of inflammatory bowel diseases (IBDs) and is associated with worse outcome. Variable rates of colectomy have been reported among IBD complicated by CDI. We conducted a systematic review and meta-analysis of studies to assess the association betwe...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析,评审

    doi:10.1097/MIB.0000000000000998

    authors: Chen Y,Furuya-Kanamori L,Doi SA,Ananthakrishnan AN,Kirk M

    更新日期:2017-02-01 00:00:00

  • Short pediatric Crohn's disease activity index for quality improvement and observational research.

    abstract:BACKGROUND:Practical and objective instruments to assess pediatric Crohn's disease (CD) activity are required for observational research and quality improvement. The objectives were: 1) to determine the feasibility of completing the Pediatric Crohn's Disease Activity Index (PCDAI) and the Abbreviated PCDAI (APCDAI); an...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21452

    authors: Kappelman MD,Crandall WV,Colletti RB,Goudie A,Leibowitz IH,Duffy L,Milov DE,Kim SC,Schoen BT,Patel AS,Grunow J,Larry E,Fairbrother G,Margolis P

    更新日期:2011-01-01 00:00:00

  • Health-related quality of life in patients with ulcerative colitis after a 10-year disease course: results from the IBSEN study.

    abstract:BACKGROUND:Ulcerative colitis (UC) negatively affects health-related quality of life (HRQoL), but population-based and long-term data on this topic are scarce. Our aim was to determine the HRQoL in UC patients after a 10-year disease duration. METHODS:UC patients from a population-based inception cohort met at a presc...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21863

    authors: Hoivik ML,Moum B,Solberg IC,Cvancarova M,Hoie O,Vatn MH,Bernklev T,IBSEN Study Group.

    更新日期:2012-08-01 00:00:00

  • Combination of innate and adaptive immune alterations increased the likelihood of fibrostenosis in Crohn's disease.

    abstract:BACKGROUND:Mutations in the nucleotide oligomerization domain-2 (NOD2) gene and positive antibodies to microbial antigens have been found to be associated with the Crohn's disease (CD) phenotype, fibrostenosis. The aim of this study was to confirm these relationships in a large cohort of CD patients and to determine th...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21196

    authors: Ippoliti A,Devlin S,Mei L,Yang H,Papadakis KA,Vasiliauskas EA,McGovern DP,Abreu MT,Melmed G,Shaye O,Enayati P,Chen G,Choi J,Taylor K,Landers CJ,Rotter JI,Targan SR

    更新日期:2010-08-01 00:00:00

  • Apical Periodontitis in Patients With Inflammatory Bowel Disease: A Puppet Master?

    abstract::Focal infection theory posits that periodontal pathobionts play a causal role in initiating or exacerbating diseases. Periodontal disease is a common inflammatory, multifactorial disease of the periodontal tissues. The main factor for inflammation is mature dental plaque with the presence of pathogens in the microbial...

    journal_title:Inflammatory bowel diseases

    pub_type: 评论,社论

    doi:10.1093/ibd/izz129

    authors: Barta Z

    更新日期:2020-01-06 00:00:00

  • Endocytosis of Intestinal Tight Junction Proteins: In Time and Space.

    abstract::Eukaryotic cells take up macromolecules and particles from the surrounding milieu and also internalize membrane proteins via a precise process of endocytosis. The role of endocytosis in diverse physiological processes such as cell adhesion, cell signaling, tissue remodeling, and healing is well recognized. The epithel...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa141

    authors: Nighot P,Ma T

    更新日期:2021-01-19 00:00:00

  • Differentiation Between Pediatric Irritable Bowel Syndrome and Inflammatory Bowel Disease Based on Fecal Scent: Proof of Principle Study.

    abstract:Background:The diagnostic work-up of pediatric irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) commonly includes invasive tests for discrimination from inflammatory bowel disease (IBD). As this carries a high burden on patients, an ongoing need exists for development of no...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy151

    authors: Bosch S,van Gaal N,Zuurbier RP,Covington JA,Wicaksono AN,Biezeveld MH,Benninga MA,Mulder CJ,de Boer NKH,de Meij TGJ

    更新日期:2018-10-12 00:00:00

  • Fecal Calprotectin Predicts Relapse and Histological Mucosal Healing in Ulcerative Colitis.

    abstract:BACKGROUND:Mucosal healing in ulcerative colitis leads to a decreased need for medication and decreased risk of disease relapse and colectomy. Histological healing seems to improve the disease prognosis even further. An assessment of both endoscopic and histological mucosal healing requires endoscopy, and the need for ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000736

    authors: Theede K,Holck S,Ibsen P,Kallemose T,Nordgaard-Lassen I,Nielsen AM

    更新日期:2016-05-01 00:00:00

  • Decreased lymphatic vessel density is associated with postoperative endoscopic recurrence in Crohn's disease.

    abstract:BACKGROUND:Increased lymphatic vessel (LV) density has been found in uninflamed intestinal wall of patients with Crohn's disease (CD). The goal of the study was to search for an association between LV density in the proximal ileal resection margin at the time of surgery and endoscopic recurrence. METHODS:Ileocolonic r...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0b013e3182971cec

    authors: Rahier JF,Dubuquoy L,Colombel JF,Jouret-Mourin A,Delos M,Ferrante M,Sokol H,Hertogh GD,Salleron J,Geboes K,Desreumaux P

    更新日期:2013-09-01 00:00:00