Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease
Publication Date
August 22, 2011
Journal
PLOS ONE
Authors
Rian M. Nijmeijer, Raffaella M. Gadaleta, Saskia W. C. Van Mil, Adriaan A. Van Bodegraven, et al
Volume
6
Issue
8
Pages
e23745
DOI
https://dx.plos.org/10.1371/journal.pone.0023745
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0023745
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21887309
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161760
Europe PMC
http://europepmc.org/abstract/MED/21887309
Web of Science
000294251800027
Scopus
80051940457
Mendeley
http://www.mendeley.com/research/farnesoid-x-receptor-fxr-activation-fxr-genetic-variation-inflammatory-bowel-disease
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Mendeley | Further Information

{"title"=>"Farnesoid X receptor (FXR) activation and FXR genetic variation in inflammatory bowel disease", "type"=>"journal", "authors"=>[{"first_name"=>"Rian M.", "last_name"=>"Nijmeijer", "scopus_author_id"=>"6603532650"}, {"first_name"=>"Raffaella M.", "last_name"=>"Gadaleta", "scopus_author_id"=>"36019889800"}, {"first_name"=>"Saskia W.C.", "last_name"=>"van Mil", "scopus_author_id"=>"6506921690"}, {"first_name"=>"Adriaan A.", "last_name"=>"van Bodegraven", "scopus_author_id"=>"35399933600"}, {"first_name"=>"J. Bart A.", "last_name"=>"Crusius", "scopus_author_id"=>"7004825435"}, {"first_name"=>"Gerard", "last_name"=>"Dijkstra", "scopus_author_id"=>"7003514792"}, {"first_name"=>"Daan W.", "last_name"=>"Hommes", "scopus_author_id"=>"7004828829"}, {"first_name"=>"Dirk J.", "last_name"=>"de Jong", "scopus_author_id"=>"16405231700"}, {"first_name"=>"Pieter C.F.", "last_name"=>"Stokkers", "scopus_author_id"=>"6701620145"}, {"first_name"=>"Hein W.", "last_name"=>"Verspaget", "scopus_author_id"=>"7005772169"}, {"first_name"=>"Rinse K.", "last_name"=>"Weersma", "scopus_author_id"=>"8238994000"}, {"first_name"=>"C. Janneke", "last_name"=>"van der Woude", "scopus_author_id"=>"8985378500"}, {"first_name"=>"Janneke M.", "last_name"=>"Stapelbroek", "scopus_author_id"=>"6508223107"}, {"first_name"=>"Marguerite E.I.", "last_name"=>"Schipper", "scopus_author_id"=>"7005487688"}, {"first_name"=>"Cisca", "last_name"=>"Wijmenga", "scopus_author_id"=>"7005273061"}, {"first_name"=>"Karel J.", "last_name"=>"van Erpecum", "scopus_author_id"=>"7006902718"}, {"first_name"=>"Bas", "last_name"=>"Oldenburg", "scopus_author_id"=>"55204246800"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"80051940457", "doi"=>"10.1371/journal.pone.0023745", "pui"=>"362390087", "pmid"=>"21887309", "scopus"=>"2-s2.0-80051940457", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"0989cee8-f2dd-3aff-971b-eb73cc9e5583", "abstract"=>"BACKGROUND: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls. RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD. CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients.", "link"=>"http://www.mendeley.com/research/farnesoid-x-receptor-fxr-activation-fxr-genetic-variation-inflammatory-bowel-disease", "reader_count"=>32, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>7, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>7, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>13, "Medicine and Dentistry"=>11, "Chemistry"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Netherlands"=>1, "Argentina"=>1, "Denmark"=>1, "France"=>1}, "group_count"=>1}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/743812"], "description"=>"<p>Montreal classification and medication of patients of the mRNA expression study.</p>", "links"=>[], "tags"=>["classification", "patients", "mrna"], "article_id"=>414167, "categories"=>["Biological Sciences", "Microbiology", "Chemistry", "Immunology", "Molecular Biology", "Genetics"], "users"=>["Rian M. Nijmeijer", "Raffaella M. Gadaleta", "Saskia W. C. van Mil", "Adriaan A. van Bodegraven", "J. Bart A. Crusius", "Gerard Dijkstra", "Daan W. Hommes", "Dirk J. de Jong", "Pieter C. F. Stokkers", "Hein W. Verspaget", "Rinse K. Weersma", "C. Janneke van der Woude", "Janneke M. Stapelbroek", "Marguerite E. I. Schipper", "Cisca Wijmenga", "Karel J. van Erpecum", "Bas Oldenburg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023745.t001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Montreal_classification_and_medication_of_patients_of_the_mRNA_expression_study_/414167", "title"=>"Montreal classification and medication of patients of the mRNA expression study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-08-22 01:09:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/743654"], "description"=>"<p>Scatter plot of mRNA expression of <i>FXR</i> and <i>SHP</i> in the ileal mucosa of healthy controls (circles), ulcerative colitis (triangles) and Crohn's disease patients (squares). Horizontal lines indicate mean values. *p<0.05 compared to healthy controls.</p>", "links"=>[], "tags"=>["patients"], "article_id"=>414012, "categories"=>["Biological Sciences", "Microbiology", "Chemistry", "Immunology", "Molecular Biology", "Genetics"], "users"=>["Rian M. Nijmeijer", "Raffaella M. Gadaleta", "Saskia W. C. van Mil", "Adriaan A. van Bodegraven", "J. Bart A. Crusius", "Gerard Dijkstra", "Daan W. Hommes", "Dirk J. de Jong", "Pieter C. F. Stokkers", "Hein W. Verspaget", "Rinse K. Weersma", "C. Janneke van der Woude", "Janneke M. Stapelbroek", "Marguerite E. I. Schipper", "Cisca Wijmenga", "Karel J. van Erpecum", "Bas Oldenburg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023745.g001", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FXR_target_gene_expression_is_decreased_in_patients_with_Crohn_s_disease_/414012", "title"=>"FXR target gene expression is decreased in patients with Crohn's disease.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-22 01:06:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/743732"], "description"=>"<p>Ileal mRNA expression of <i>SI</i>, <i>FXR</i> and <i>SHP</i> were related by regression analyses to ileal mRNA expression of differentiation marker <i>Villin</i> in healthy controls (A, D, G), ulcerative colitis (B, E, H) and Crohn's disease patients (C, F, I). Spearman's coefficients and p values are shown. Values in bold show statistically significant correlations; *p<0.05; **p<0.01, ***p<0.001.</p>", "links"=>[], "tags"=>["shp", "correlate", "villin", "controls"], "article_id"=>414086, "categories"=>["Biological Sciences", "Microbiology", "Chemistry", "Immunology", "Molecular Biology", "Genetics"], "users"=>["Rian M. Nijmeijer", "Raffaella M. Gadaleta", "Saskia W. C. van Mil", "Adriaan A. van Bodegraven", "J. Bart A. Crusius", "Gerard Dijkstra", "Daan W. Hommes", "Dirk J. de Jong", "Pieter C. F. Stokkers", "Hein W. Verspaget", "Rinse K. Weersma", "C. Janneke van der Woude", "Janneke M. Stapelbroek", "Marguerite E. I. Schipper", "Cisca Wijmenga", "Karel J. van Erpecum", "Bas Oldenburg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023745.g002", "stats"=>{"downloads"=>1, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FXR_and_SHP_correlate_with_Villin_in_healthy_controls_but_not_in_Crohn_s_disease_patients_/414086", "title"=>"FXR and SHP correlate with Villin in healthy controls but not in Crohn's disease patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-22 01:08:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/374987", "https://ndownloader.figshare.com/files/375028", "https://ndownloader.figshare.com/files/375070", "https://ndownloader.figshare.com/files/375113", "https://ndownloader.figshare.com/files/375155", "https://ndownloader.figshare.com/files/375195", "https://ndownloader.figshare.com/files/375233", "https://ndownloader.figshare.com/files/375267", "https://ndownloader.figshare.com/files/375316"], "description"=>"<div><h3>Background</h3><p>We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in <em>FXR</em> is associated with IBD.</p> <h3>Methods</h3><p>mRNA expression of <em>FXR</em> and FXR target gene <em>SHP</em> was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in <em>FXR</em> were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls.</p> <h3>Results</h3><p>mRNA expression of <em>SHP</em> in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker <em>Villin</em> was correlated with <em>FXR</em> and <em>SHP</em> in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD.</p> <h3>Conclusions</h3><p>FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in <em>FXR</em>. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients.</p> </div>", "links"=>[], "tags"=>["farnesoid", "receptor", "activation", "fxr", "inflammatory", "bowel"], "article_id"=>134047, "categories"=>["Biological Sciences", "Microbiology", "Chemistry", "Immunology", "Molecular Biology", "Genetics"], "users"=>["Rian M. Nijmeijer", "Raffaella M. Gadaleta", "Saskia W. C. van Mil", "Adriaan A. van Bodegraven", "J. Bart A. Crusius", "Gerard Dijkstra", "Daan W. Hommes", "Dirk J. de Jong", "Pieter C. F. Stokkers", "Hein W. Verspaget", "Rinse K. Weersma", "C. Janneke van der Woude", "Janneke M. Stapelbroek", "Marguerite E. I. Schipper", "Cisca Wijmenga", "Karel J. van Erpecum", "Bas Oldenburg"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0023745.s001", "https://dx.doi.org/10.1371/journal.pone.0023745.s002", "https://dx.doi.org/10.1371/journal.pone.0023745.s003", "https://dx.doi.org/10.1371/journal.pone.0023745.s004", "https://dx.doi.org/10.1371/journal.pone.0023745.s005", "https://dx.doi.org/10.1371/journal.pone.0023745.s006", "https://dx.doi.org/10.1371/journal.pone.0023745.s007", "https://dx.doi.org/10.1371/journal.pone.0023745.s008", "https://dx.doi.org/10.1371/journal.pone.0023745.s009"], "stats"=>{"downloads"=>58, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Farnesoid_X_Receptor_FXR_Activation_and_FXR_Genetic_Variation_in_Inflammatory_Bowel_Disease/134047", "title"=>"Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-08-22 01:07:27"}

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Relative Metric

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