Linked Life Data

17035595

Source:http://linkedlifedata.com/resource/pubmed/id/17035595

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-22
pubmed:abstractText
The epithelial barrier is determined primarily by intercellular tight junctions (TJs). We have demonstrated previously that all-trans retinoic acid (atRA) plays an important role in forming functional TJs through a specific retinoic acid receptor (RAR)/retinoid X receptor heterodimer in epithelial cells. However, the physiological relevance of retinoic acids (RAs) in maintaining the epithelial integrity remains to be examined. Here, we show that several types of RA, including atRA, promote the barrier function of epithelial TJs. Conversely, RA depletion in the cells by overexpressing CYP26s, cytochrome P450 enzymes specifically involved in the metabolic inactivation of RAs, induces an increase of permeability as measured by two differently sized tracer molecules, inulin and mannitol. This RA-mediated enhancement of barrier function is potentially associated with the increased expression of TJ-associated genes such as occludin, claudin-1, claudin-4, and zonula occludens-1. We also found that RARalpha is a preferential regulator of the epithelial barrier in vitro. Studies of murine experimental colitis, which is characterized by increased gut permeability, reveal that RARalpha stimulation significantly attenuates the loss of the epithelial barrier during colitis in vivo. Our results suggest that cellular RA bioavailability determines the epithelial integrity, because it is a critical regulator for barrier protection during mucosal injuries.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
250-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Cellular retinoic acid bioavailability determines epithelial integrity: Role of retinoic acid receptor alpha agonists in colitis.
pubmed:affiliation
Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Sapporo, Japan. osanaim@sapmed.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't