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http://purl.uniprot.org/citations/18687707http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18687707http://www.w3.org/2000/01/rdf-schema#comment"

Background

Colon epithelial cell (CEC) apoptosis and nuclear factor-kappaB (NF-kappaB) activation may compromise barrier function, and it has been reported that signal transducer and activator of transcription 5b (STAT5b)-deficient mice exhibit increased susceptibility to colitis. It is hypothesised that the growth hormone (GH) target STAT5b maintains mucosal barrier integrity by promoting CEC survival and inhibiting NF-kappaB activation.

Methods

The GH effect upon mucosal injury due to 2,4,6-trinitro-benzenesulfonic acid (TNBS) administration was determined in STAT5b-deficient mice and wild-type (WT) controls. The effect of STAT5b deficiency upon CEC survival and NF-kappaB activation was determined and related to differences in intestinal permeability and bacterial translocation. RNA interference (RNAi) was used to knock down STAT5b expression in the T84 CEC line, and the effect upon basal and GH-dependent regulation of proapoptotic and inflammatory pathways induced by tumour necrosis factor alpha (TNFalpha) was determined.

Results

GH suppression of mucosal inflammation in TNBS colitis was abrogated in STAT5b-deficient mice. STAT5b deficiency led to activation of a proapoptotic pattern of gene expression in the colon, and increased mucosal permeability. The frequency of apoptotic CECs was increased in STAT5b-deficient mice while tight junction protein abundance was reduced. This was associated with upregulation of CEC Toll-like receptor 2 expression and NF-kappaB activation. STAT5b knockdown in T84 CEC increased TNFalpha-dependent NF-kappaB and caspase-3 activation. GH inhibition of TNFalpha signalling was prevented by STAT5b knockdown.

Conclusion

STAT5b maintains colonic barrier integrity by modulating CEC survival and NF-kappaB activation. STAT5b activation may therefore represent a novel therapeutic target in inflammatory bowel disease."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.org/dc/terms/identifier"doi:10.1136/gut.2007.145094"xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Han X."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Ren X."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Xu H."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Hogan S.P."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Wilson T.A."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Denson L.A."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Groschwitz K."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Jurickova I."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/author"Pasternak B.A."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/name"Gut"xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/pages"49-58"xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/title"Regulation of intestinal barrier function by signal transducer and activator of transcription 5b."xsd:string
http://purl.uniprot.org/citations/18687707http://purl.uniprot.org/core/volume"58"xsd:string
http://purl.uniprot.org/citations/18687707http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18687707
http://purl.uniprot.org/citations/18687707http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18687707
http://purl.uniprot.org/uniprot/#_P42232-mappedCitation-18687707http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18687707
http://purl.uniprot.org/uniprot/#_Q9CTB3-mappedCitation-18687707http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18687707
http://purl.uniprot.org/uniprot/P42232http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18687707
http://purl.uniprot.org/uniprot/Q9CTB3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18687707