Abstract:
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.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Zhang YG,Lu R,Xia Y,Zhou D,Petrof E,Claud EC,Sun Jdoi
10.1093/ibd/izy292subject
Has Abstractpub_date
2019-01-01 00:00:00pages
97-110issue
1eissn
1078-0998issn
1536-4844pii
5115658journal_volume
25pub_type
杂志文章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
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更新日期:2011-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20128
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析,评审
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更新日期:2017-02-01 00:00:00
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
doi:10.1097/MIB.0000000000001070
更新日期:2017-05-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e3182802909
更新日期:2013-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
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doi:10.1097/MIB.0000000000000864
更新日期:2016-09-01 00:00:00
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
doi:10.1002/ibd.20423
更新日期:2008-08-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21317
更新日期:2010-12-01 00:00:00
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
doi:10.1002/ibd.21227
更新日期:2010-11-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21336
更新日期:2011-01-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200405000-00002
更新日期:2004-05-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000436275.12131.4f
更新日期:2014-01-01 00:00:00
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
doi:10.1002/ibd.21851
更新日期:2012-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1097/MIB.0000000000001073
更新日期:2017-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200005000-00007
更新日期:2000-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/ibd/izz260
更新日期:2020-06-18 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000731
更新日期:2016-06-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21563
更新日期:2011-10-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20242
更新日期:2007-12-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2010-11-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2017-12-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21911
更新日期:2012-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/ibd/izx012
更新日期:2017-12-19 00:00:00
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pub_type: 杂志文章
doi:10.1093/ibd/izz144
更新日期:2020-03-04 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000118
更新日期:2014-08-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.22948
更新日期:2013-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1097/MIB.0000000000001222
更新日期:2017-09-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21932
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
doi:10.1097/01.MIB.0000435440.22484.e8
更新日期:2013-12-01 00:00:00