Lack of Vitamin D Receptor Leads to Hyperfunction of Claudin-2 in Intestinal Inflammatory Responses.


Background:Vitamin D3 and vitamin D receptor (VDR) are involved in the pathogenesis of inflammatory bowel disease (IBD) and bacterial infection. Claudin-2 is a junction protein that mediates paracellular water transport in epithelia. Elevation of Claudin-2 is associated with active IBD. However, VDR involved in epithelial junctions under inflammation and infection remains largely unknown. We investigated the mechanisms on how VDR and Claudin-2 are related in inflamed states. Methods:Using cultured VDR-/- enteroids, human intestinal epithelial cells, VDR-/- mice with Salmonella- or DSS-colitis, and human IBD samples, we investigated the mechanisms how VDR and Claudin-2 are related in inflamed states. Results:After Salmonella infection had taken place, we observed significantly enhanced Claudin-2 and an increased bacterial invasion and translocation. A lack of VDR regulation led to a robust increase of Claudin-2 at the mRNA and protein levels post-infection. In DSS-treated VDR-/- mice, Claudin-2 was significantly increased. Location and quantification of Claudin-2 protein in the mouse colons treated with DSS also confirmed these results. Inflammatory cytokines were significantly higher in the serum and mRNA levels in intestine, which are known to increase Claudin-2. Furthermore, in inflamed intestine of ulcerative colitis patients, VDR expression was low and Claudin-2 was enhanced. Mechanistically, we identified the enhanced Claudin-2 promoter activity through the binding sites of NF-κB and STAT in inflamed VDR-/- cells. Conclusions:Our studies have identified a new role for intestinal epithelial VDR in regulating barrier functions in the context of infection and inflammation.


Inflamm Bowel Dis


Zhang YG,Lu R,Xia Y,Zhou D,Petrof E,Claud EC,Sun J




Has Abstract


2019-01-01 00:00:00














  • Proteomic profiling of mucosal and submucosal colonic tissues yields protein signatures that differentiate the inflammatory colitides.

    abstract:BACKGROUND:Differentiating ulcerative colitis (UC) from Crohn's colitis (CC) can be difficult and may lead to inaccurate diagnoses in up to 30% of inflammatory bowel disease (IBD) patients. Much of the diagnostic uncertainty arises from the overlap of clinical and histologic features. Matrix-assisted laser desorption/i...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: M'Koma AE,Seeley EH,Washington MK,Schwartz DA,Muldoon RL,Herline AJ,Wise PE,Caprioli RM

    更新日期:2011-04-01 00:00:00

  • Validation of the mainland Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) for ulcerative colitis and Crohn's disease.

    abstract:BACKGROUND:Inflammatory bowel disease affects the quality of a patient's life in many ways, but no validated instrument for measuring disease-specific quality of life in these patients is available for use in Mainland China. The aim of our study was to develop and validate the Mainland Chinese translation of the Inflam...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Ren WH,Lai M,Chen Y,Irvine EJ,Zhou YX

    更新日期:2007-07-01 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


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

    更新日期:2017-02-01 00:00:00

  • Etiopathogenesis of Nephrolithiasis in Ulcerative Colitis Patients with the Ileal Pouch Anal Anastomosis.

    abstract:BACKGROUND:Our previous study showed that nephrolithiasis is a common complication in ulcerative colitis patients after ileal pouch anal anastomosis (IPAA). However, the pathogenesis of nephrolithiasis in IPAA patients has not been studied. The aim of this study was to compare urine and serum metabolic compositions in ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Arora Z,Mukewar S,Lopez R,Camino D,Shen B,Hall P

    更新日期:2017-05-01 00:00:00

  • Infliximab in steroid-dependent ulcerative colitis: effectiveness and predictors of clinical and endoscopic remission.

    abstract:BACKGROUND:Up to 20% of patients with ulcerative colitis (UC) become steroid-dependent during their course. Thiopurines are recommended in steroid-dependent UC, but their efficacy is debated. Data exploring the use of infliximab in these patients are scarce. Aims of this study were to evaluate the effectiveness of infl...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Armuzzi A,Pugliese D,Danese S,Rizzo G,Felice C,Marzo M,Andrisani G,Fiorino G,Sociale O,Papa A,De Vitis I,Rapaccini GL,Guidi L

    更新日期:2013-04-01 00:00:00

  • Patient-reported Anxiety: A Possible Predictor of Pediatric Inflammatory Bowel Disease Health Care Use.

    abstract:BACKGROUND:Anxiety is linked with adverse health-related outcomes and increased health-seeking behaviors among patients with chronic illness. Yet, this relationship has received little attention in pediatric inflammatory bowel disease. The aim of this study was to examine whether anxiety symptoms predicted youth at inc...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Reigada LC,Satpute A,Hoogendoorn CJ,Cohen BH,Lai J,Bao R,Dubinsky MC,Benkov KJ

    更新日期:2016-09-01 00:00:00

  • Crohn's disease-associated Escherichia coli LF82 aggravates colitis in injured mouse colon via signaling by flagellin.

    abstract:BACKGROUND:Ileal lesions in Crohn's disease patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) that harbor various virulence factors involved in adhesion to and invasion of intestinal epithelial cultured cells. We investigated in a mouse model of colonic inflammation the behavior of virulent...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Carvalho FA,Barnich N,Sauvanet P,Darcha C,Gelot A,Darfeuille-Michaud A

    更新日期:2008-08-01 00:00:00

  • Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase.

    abstract:BACKGROUND:The proinflammatory effect of high-fat diet has been observed beyond the cardiovascular system, but there is little evidence to support its role in triggering inflammatory bowel disease. GPx1/2-double-knockout (DKO) mice deficient in 2 intracellular glutathione peroxidases, GPx1 and GPx2, on a C57BL/6 (B6) b...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Gao Q,Esworthy RS,Kim BW,Synold TW,Smith DD,Chu FF

    更新日期:2010-12-01 00:00:00

  • Dysplastic lesions in ulcerative colitis: changing paradigms.

    abstract::Crohn and Rosenberg first highlighted the increased risk of colorectal cancer in ulcerative colitis in 1925. Cancer rates as high as 34 percent after 30 yrs of disease have been reported in several population-based studies, although the reported risk varies substantially. Lower rates have been reported in: population-...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Allen PB,Kamm MA,De Cruz P,Desmond PV

    更新日期:2010-11-01 00:00:00

  • Liver diseases associated with anti-tumor necrosis factor-alpha (TNF-α) use for inflammatory bowel disease.

    abstract::The conventional treatment of inflammatory bowel disease (IBD) has focused on nonspecifically targeting mucosal inflammation. In the last decade, with the advent of novel biological agents that directly inhibit proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), rapid progress has been made in clin...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Coffin CS,Fraser HF,Panaccione R,Ghosh S

    更新日期:2011-01-01 00:00:00

  • Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis.

    abstract:BACKGROUND:FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In t...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Mizushima T,Ito T,Kishi D,Kai Y,Tamagawa H,Nezu R,Kiyono H,Matsuda H

    更新日期:2004-05-01 00:00:00

  • High residential sun exposure is associated with a low risk of incident Crohn's disease in the prospective E3N cohort.

    abstract:BACKGROUND:Vitamin D insufficiency has been suggested to be associated with high risk of Crohn's disease (CD). In France, where food fortification is limited, the major source of vitamin D is through sun exposure. The aim of this work was to analyze the relationship between residential sun exposure and the risk of inci...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Jantchou P,Clavel-Chapelon F,Racine A,Kvaskoff M,Carbonnel F,Boutron-Ruault MC

    更新日期:2014-01-01 00:00:00

  • Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1.

    abstract:BACKGROUND:Genetic variants of nucleotide-binding oligomerization domain 2 (NOD2) lead to aberrant microbial recognition and can cause chronic inflammatory diseases in patients with Crohn's disease (CD). METHODS:We utilized gene-specific siRNA mediated knockdown and expression of guanine nucleotide exchange factor H1 ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Zhao Y,Alonso C,Ballester I,Song JH,Chang SY,Guleng B,Arihiro S,Murray PJ,Xavier R,Kobayashi KS,Reinecker HC

    更新日期:2012-04-01 00:00:00

  • 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


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

    更新日期:2017-04-01 00:00:00

  • Probiotics and inflammatory bowel disease: is there a scientific rationale?

    abstract::Most conventional forms of drug therapy suppress or modify the host immunoinflammatory response and neglect the other contributor to disease pathogenesis-the environmental microflora. Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health. The rationale ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Shanahan F

    更新日期:2000-05-01 00:00:00

  • Stigma and Disclosure in Patients With Inflammatory Bowel Disease.

    abstract::Stigma in patients suffering from chronic disease is associated with worse clinical outcomes and secondary medical issues such as depression, anxiety, and decreased quality of life. We believe various forms of stigma can have different clinical significance in patients with inflammatory bowel disease (IBD). With furth...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Guo L,Rohde J,Farraye FA

    更新日期:2020-06-18 00:00:00

  • A Critical Role for Monocytes/Macrophages During Intestinal Inflammation-associated Lymphangiogenesis.

    abstract:BACKGROUND:Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL is believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known to contribute to intestinal pathology in inflammatory bowel disease, their r...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Becker F,Kurmaeva E,Gavins FN,Stevenson EV,Navratil AR,Jin L,Tsunoda I,Orr AW,Alexander JS,Ostanin DV

    更新日期:2016-06-01 00:00:00

  • Thromboembolism in pediatric inflammatory bowel disease: systematic review.

    abstract:BACKGROUND:Several studies suggest an increased risk of venous and arterial thromboembolism (TE) in adults with inflammatory bowel disease (IBD) compared to the general population. We performed a systematic review of studies on incidence and characteristic of TE in children with IBD. METHODS:We searched Medline, LILAC...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Lazzerini M,Bramuzzo M,Maschio M,Martelossi S,Ventura A

    更新日期:2011-10-01 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


    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

  • Clinical trial: a novel high-dose 1 g mesalamine suppository (Salofalk) once daily is as efficacious as a 500-mg suppository thrice daily in active ulcerative proctitis.

    abstract:BACKGROUND:Mesalamine suppositories are first-line therapy in active ulcerative proctitis; the standard regime still recommends multiple doses per day. The primary objective of this study was to show the noninferiority of once-daily administration of a novel 1 g mesalamine suppository versus thrice-daily administration...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Andus T,Kocjan A,Müser M,Baranovsky A,Mikhailova TL,Zvyagintseva TD,Dorofeyev AE,Lozynskyy YS,Cascorbi I,Stolte M,Vieth M,Dilger K,Mohrbacher R,Greinwald R,International Salofalk Suppository OD Study Group.

    更新日期:2010-11-01 00:00:00

  • Antioxidant properties of mesalamine in colitis inhibit phosphoinositide 3-kinase signaling in progenitor cells.

    abstract:BACKGROUND:Mesalamine, 5-aminosalicylic acid (5-ASA), is a potent antioxidant and is known to enhance peroxisome proliferator-activated receptor γ activity in the intestine. Our previous studies suggested reduced Phosphoinositide 3-Kinase (PI3K)/β-catenin signaling as a mechanism for 5-ASA chemoprevention in chronic ul...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Managlia E,Katzman RB,Brown JB,Barrett TA

    更新日期:2013-09-01 00:00:00

  • Rapid Infliximab Infusion in Children with Inflammatory Bowel Disease: A Multicenter North American Experience.

    abstract:BACKGROUND:Infliximab (IFX) infusion may lead to development of anti-IFX antibodies, and subsequent infusion reactions (IRs). The safety of rapid IFX infusion administered over 60 minutes has been under-investigated in children with inflammatory bowel disease. In a multicenter study, the frequency and nature of rapid i...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,多中心研究


    authors: El-Matary W,Dykes DMH,Bauman L,Elkadri A,Carroll MW,Izaguirre MR,deBruyn J,Samson CM,Crim AM,Ali S,Grossman A

    更新日期:2017-12-01 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


    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

  • Development and Validation of a Confocal Laser Endomicroscopy-Based Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients.

    abstract:Background:Endoscopic monitoring is fundamental for evaluating the therapeutic response in IBD, but a validated endomicroscopic mucosal healing (MH) score is not available to date. However, confocal laser endomicroscopy (CLE) might define MH more precisely than conventional endoscopy. The major aim was to establish and...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Hundorfean G,Chiriac MT,Mihai S,Hartmann A,Mudter J,Neurath MF

    更新日期:2017-12-19 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


    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

  • In vivo imaging of reactive oxygen and nitrogen species in murine colitis.

    abstract:BACKGROUND:Traditional techniques analyzing mouse colitis are invasive, laborious, or indirect. Development of in vivo imaging techniques for specific colitis processes would be useful for monitoring disease progression and/or treatment effectiveness. The aim was to evaluate the applicability of the chemiluminescent pr...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Asghar MN,Emani R,Alam C,Helenius TO,Grönroos TJ,Sareila O,Din MU,Holmdahl R,Hänninen A,Toivola DM

    更新日期:2014-08-01 00:00:00

  • Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease.

    abstract:BACKGROUND:Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Akbari M,Shah S,Velayos FS,Mahadevan U,Cheifetz AS

    更新日期:2013-01-01 00:00:00

  • Machine Learning-Based Gene Prioritization Identifies Novel Candidate Risk Genes for Inflammatory Bowel Disease.

    abstract:BACKGROUND:The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders, associated with genetic, immunologic, and environmental factors. Although hundreds of genes are implicated in IBD etiology, it is likely that additional genes play a role in the disease process. We developed a machine learning-based g...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Isakov O,Dotan I,Ben-Shachar S

    更新日期:2017-09-01 00:00:00

  • Incidence of and impact of medications on colectomy in newly diagnosed ulcerative colitis in the era of biologics.

    abstract:BACKGROUND:The cumulative incidence of colectomy and the impact of 5-aminosalicylates (5-ASA), azathioprine, and antitumor necrosis factor (TNF) treatment on the long-term need for surgery are unknown in ulcerative colitis (UC) in the era of biologics. METHODS:This was an observational study of a referral center cohor...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Williet N,Pillot C,Oussalah A,Billioud V,Chevaux JB,Bresler L,Bigard MA,Gueant JL,Peyrin-Biroulet L

    更新日期:2012-09-01 00:00:00

  • Comparative study of candidate housekeeping genes for quantification of target gene messenger RNA expression by real-time PCR in patients with inflammatory bowel disease.

    abstract:BACKGROUND:Mucosal expression of immunological mediators is modified in inflammatory bowel disease (IBD). Quantification of target gene messenger RNA (mRNA) transcripts depends on the normalization to a housekeeping or reference gene. Stability of housekeeping gene expression is critical for the accurate measurement of...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Bamias G,Goukos D,Laoudi E,Balla IG,Siakavellas SI,Daikos GL,Ladas SD

    更新日期:2013-12-01 00:00:00