Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-9-27
pubmed:abstractText
Transforming growth factor beta (TGF-beta) plays a critical role in the pathogenesis of the peritoneal fibrosis that complicates long-term peritoneal dialysis (PD). We studied the TGF-beta/Smad signaling pathway in peritoneal fibrosis induced in uremic rats treated with PD and explored the therapeutic potential of Smad7 to prevent fibrogenesis. After subtotal nephrectomy, uremic rats were treated with peritoneal dialysis using 4.25% dextrose-containing fluid. The peritoneum of uremic rats treated with PD demonstrated fibrosis, increased TGF-beta expression, increased Smad2/3 activation, decreased Smad7 expression, and increased expression of fibrogenic and angiogenic factors. In addition, peritoneal function was impaired and its structure was altered, including a thickened submesothelial layer. In rats transfected with a Smad7 transgene using an ultrasound-microbubble-mediated system, peritoneal fibrosis was attenuated, peritoneal function was improved, and Smad2/3 activation was inhibited. We suggest that administration of Smad7 inhibits peritoneal fibrogenesis in uremic rats treated with PD by correcting the imbalance between downregulated Smad7 and activated Smad2/3. Blockade of the TGF-beta/Smad signaling pathway may represent a novel therapeutic approach to prevent peritoneal fibrosis in patients treated with PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2689-703
pubmed:meshHeading
pubmed-meshheading:17855642-Animals, pubmed-meshheading:17855642-Extracellular Matrix, pubmed-meshheading:17855642-Fibrosis, pubmed-meshheading:17855642-Gene Expression, pubmed-meshheading:17855642-Gene Therapy, pubmed-meshheading:17855642-Male, pubmed-meshheading:17855642-Neovascularization, Pathologic, pubmed-meshheading:17855642-Peritoneal Dialysis, Continuous Ambulatory, pubmed-meshheading:17855642-Peritoneal Diseases, pubmed-meshheading:17855642-Peritoneum, pubmed-meshheading:17855642-Rats, pubmed-meshheading:17855642-Rats, Sprague-Dawley, pubmed-meshheading:17855642-Signal Transduction, pubmed-meshheading:17855642-Smad7 Protein, pubmed-meshheading:17855642-Transfection, pubmed-meshheading:17855642-Transforming Growth Factor beta, pubmed-meshheading:17855642-Transgenes, pubmed-meshheading:17855642-Uremia
pubmed:year
2007
pubmed:articleTitle
Smad7 transgene attenuates peritoneal fibrosis in uremic rats treated with peritoneal dialysis.
pubmed:affiliation
Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't