Linked Life Data

12468529

Source:http://linkedlifedata.com/resource/pubmed/id/12468529

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-2-17
pubmed:abstractText
Cholangiocytes express water channels (i.e. aquaporins (AQPs)), proteins that are increasingly recognized as important in water transport by biliary epithelia. However, direct functional studies demonstrating AQP-mediated water transport in cholangiocytes are limited, in part because of the lack of specific AQP inhibitors. To address this issue, we designed, synthesized, and utilized small interfering RNAs (siRNAs) selective for AQP1 and investigated their effectiveness in altering AQP1-mediated water transport in intrahepatic bile duct units (IBDUs) isolated from rat liver. Twenty-four hours after transfection of IBDUs with siRNAs targeting two different regions of the AQP1 transcript, both AQP1 mRNA and protein expression were inhibited by 76.6-92.0 and 57.9-79.4%, respectively. siRNAs containing the same percent of base pairs as the AQP1-siRNAs but in random sequence (i.e. scrambled siRNAs) had no effect. Suppression of AQP1 expression in cholangiocytes resulted in a decrease in water transport by IBDUs in response to both an inward osmotic gradient (200 mosm) or a secretory agonist (forskolin), the osmotic water permeability coefficient (P(f)) decreasing up to 58.8% and net water secretion (J(v)) decreasing up to 87%. A strong correlation between AQP1 protein expression and water transport in IBDUs transfected with AQP1-siRNAs was consistent with the decrease in water transport by IBDUs resulting from AQP1 gene silencing by AQP1-siRNAs. This study is the first to demonstrate the feasibility of utilizing siRNAs to specifically reduce the expression of AQPs in epithelial cells and provides direct evidence of the contribution of AQP1 to water transport by biliary epithelia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6268-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Specific inhibition of AQP1 water channels in isolated rat intrahepatic bile duct units by small interfering RNAs.
pubmed:affiliation
Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic, and Foundation, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't