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rdf:type |
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lifeskim:mentions |
umls-concept:C0018837,
umls-concept:C0035820,
umls-concept:C0041904,
umls-concept:C0162493,
umls-concept:C0178539,
umls-concept:C0220905,
umls-concept:C0250400,
umls-concept:C0282498,
umls-concept:C0441712,
umls-concept:C1171362,
umls-concept:C1521991
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pubmed:issue |
3
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pubmed:dateCreated |
2008-2-29
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pubmed:abstractText |
The heat stress (HS)-induced increase in occludin protein expression has been postulated to be a protective response against HS-induced disruption of the intestinal epithelial tight junction barrier. The aim of this study was to elucidate the cellular and molecular processes that mediate the HS-induced up-regulation of occludin expression in Caco-2 cells. Exposure to HS (39 degrees C or 41 degrees C) resulted in increased expression of occludin protein; this was preceded by an increase in occludin mRNA transcription and promoter activity. HS-induced activation of heat shock factor-1 (HSF-1) resulted in cytoplasmic-to-nuclear translocation of HSF-1 and binding to its binding motif in the occludin promoter region. HSF-1 activation was associated with an increase in occludin promoter activity, mRNA transcription, and protein expression; which were abolished by the HSF-1 inhibitor quercetin. Targeted HSF-1 knock-down by siRNA transfection inhibited the HSF-1-induced increase in occulin expression and junctional localization of occulin protein. Site-directed mutagenesis of the HSF-1 binding motif in the occludin promoter region inhibited HS-induced binding of HSF-1 to the occludin promoter region and subsequent promoter activity. In conclusion, our data show for the first time that the HS-induced increase in occludin protein expression is mediated by HSF-1 activation and subsequent binding of HSF-1 to the occludin promoter, which initiates a series of molecular and cellular events culminating in increased junctional localization of occludin protein.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18276783-10361874,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18276783-9920768
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
172
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
659-70
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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