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














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    abstract:BACKGROUND:If dysplasia is found on biopsies during surveillance colonoscopy for ulcerative colitis (UC), many experts recommend colectomy given the substantial risk of synchronous colon cancer. The objective was to learn if UC patients' perceptions of their colon cancer risk and if their preferences for elective colec...

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    pub_type: 杂志文章,多中心研究


    authors: Siegel CA,Schwartz LM,Woloshin S,Cole EB,Rubin DT,Vay T,Baars J,Sands BE

    更新日期:2010-10-01 00:00:00

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    journal_title:Inflammatory bowel diseases

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    更新日期:2009-05-01 00:00:00

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    abstract:BACKGROUND:Previous controversy was generated over the hypothesis that a paramyxovirus such as measles or vaccination against such viruses might be causally associated with inflammatory bowel disease (IBD). We aimed to determine if Crohn's disease (CD) or ulcerative colitis (UC) subjects are more likely to be seroposit...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Bernstein CN,Rawsthorne P,Blanchard JF

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Hyams J,Markowitz J,Treem W,Davis P,Grancher K,Daum F

    更新日期:1995-04-01 00:00:00

  • Etiology of pouchitis.

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    journal_title:Inflammatory bowel diseases

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    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

  • Totally laparoscopic total proctocolectomy: a safe alternative to open surgery in inflammatory bowel disease.

    abstract:BACKGROUND:Inflammatory bowel disease (IBD) patients have a high incidence of wound and overall postoperative complications. A totally laparoscopic approach could potentially reduce these risks. We adopted totally laparoscopic total proctocolectomy (TL-TPC) using the perineal wound for extraction as the procedure of ch...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Holder-Murray J,Zoccali M,Hurst RD,Umanskiy K,Rubin M,Fichera A

    更新日期:2012-05-01 00:00:00

  • Minimally invasive colectomy for Crohn's colitis: a single institution experience.

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Holubar SD,Dozois EJ,Privitera A,Pemberton JH,Cima RR,Larson DW

    更新日期:2010-11-01 00:00:00

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    authors: van Schaik FD,Oldenburg B,Offerhaus GJ,Schipper ME,Vleggaar FP,Siersema PD,van Oijen MG,Ten Kate FJ

    更新日期:2012-03-01 00:00:00

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    journal_title:Inflammatory bowel diseases

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

    更新日期:2016-05-01 00:00:00

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    abstract:BACKGROUND:The presumed etiology and prevalence of pancreatic abnormalities in patients with ulcerative colitis (UC) have been controversial. We conducted a controlled (cross-sectional) study of patients with UC compared with non-UC controls to determine the prevalence of pancreatic duct abnormalities in patients with ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Toda N,Akahane M,Kiryu S,Matsubara Y,Yamaji Y,Okamoto M,Minagawa N,Ohgi K,Komatsu Y,Yahagi N,Yoshida H,Kawabe T,Ohtomo K,Omata M

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: McCurdy JD,Enders FT,Khanna S,Bruining DH,Jones A,Killian JM,Tariq R,Smyrk TC,Loftus EV Jr

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    pub_type: 杂志文章


    authors: Kooros K,Katz AJ

    更新日期:2004-07-01 00:00:00

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Lund JL,Stürmer T,Porter CQ,Sandler RS,Kappelman MD

    更新日期:2011-03-01 00:00:00

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析,评审


    authors: Bettenworth D,Gustavsson A,Atreja A,Lopez R,Tysk C,van Assche G,Rieder F

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    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

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Sorrentino D,Nguyen VQ

    更新日期:2018-06-08 00:00:00

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    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

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    journal_title:Inflammatory bowel diseases

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    authors: Wang W,Jovel J,Halloran B,Wine E,Patterson J,Ford G,OʼKeefe S,Meng B,Song D,Zhang Y,Tian Z,Wasilenko ST,Rahbari M,Reza S,Mitchell T,Jordan T,Carpenter E,Madsen K,Fedorak R,Dielemann LA,Ka-Shu Wong G,Mason AL

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Fuller-Thomson E,West KJ,Sulman J,Baird SL

    更新日期:2015-11-01 00:00:00

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    journal_title:Inflammatory bowel diseases

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    authors: Meenan J,Oʼhallinan E,Scott J,Weir DG

    更新日期:1996-10-01 00:00:00

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Suenaert P,Maerten P,Van Assche G,Van Driessche W,Geboes K,Bulteel V,Simaels J,Augustijns P,Ceuppens JL,Rutgeerts P,Perrier C

    更新日期:2010-08-01 00:00:00

  • Risk Factors and Clinical Outcomes Associated with Cytomegalovirus Colitis in Patients with Acute Severe Ulcerative Colitis.

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Lee HS,Park SH,Kim SH,Kim J,Choi J,Lee HJ,Kim WS,Lee JM,Kwak MS,Hwang SW,Yang DH,Kim KJ,Ye BD,Byeon JS,Myung SJ,Yoon YS,Yu CS,Kim JH,Yang SK

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    journal_title:Inflammatory bowel diseases

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    authors: Barnes EL,Jiang Y,Kappelman MD,Long MD,Sandler RS,Kinlaw AC,Herfarth HH

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Sciola V,Massironi S,Conte D,Caprioli F,Ferrero S,Ciafardini C,Peracchi M,Bardella MT,Piodi L

    更新日期:2009-06-01 00:00:00

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Shi J,Zhou L,Zhernakova A,Qian J,Zhu F,Sun G,Zhu L,Ma X,Dijkstra G,Wijmenga C,Faber KN,Lu X,Weersma RK

    更新日期:2011-12-01 00:00:00

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Huybers S,Apostolaki M,van der Eerden BC,Kollias G,Naber TH,Bindels RJ,Hoenderop JG

    更新日期:2008-06-01 00:00:00

  • Toward an Algorithm for the Diagnosis and Management of CMV in Patients with Colitis.

    abstract:INTRODUCTION:Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the managem...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Beswick L,Ye B,van Langenberg DR

    更新日期:2016-12-01 00:00:00

  • Smoking habits in patients with ulcerative colitis: evaluation of retrospective questionnaires.

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Tysk C,Järnerot G

    更新日期:1995-07-01 00:00:00

  • Factors Associated with Discontinuation of Anti-TNF Inhibitors Among Persons with IBD: A Population-Based Analysis.

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Targownik LE,Tennakoon A,Leung S,Lix LM,Nugent Z,Singh H,Bernstein CN

    更新日期:2017-03-01 00:00:00

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

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    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    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