Linked Life Data

21056957

Source:http://linkedlifedata.com/resource/pubmed/id/21056957

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-2-2
pubmed:abstractText
Pulmonary fibrosis (PF) is characterized by increased deposition of proteoglycans (PGs), in particular core proteins. Glycosaminoglycans (GAGs) are key players in tissue repair and fibrosis, and we investigated whether PF is associated with changes in the expression and structure of GAGs as well as in the expression of ?1,3-glucuronosyltransferase I (GlcAT-I), a rate-limiting enzyme in GAG synthesis. Lung biopsies from idiopathic pulmonary fibrosis (IPF) patients and lung tissue from a rat model of bleomycin (BLM)-induced PF were immunostained for chondroitin sulfated-GAGs and GlcAT-I expression. Alterations in disaccharide composition and sulfation of chondroitin/dermatan sulfate (CS/DS) were evaluated by fluorophore-assisted carbohydrate electrophoresis (FACE) in BLM rats. Lung fibroblasts isolated from control (saline-instilled) or BLM rat lungs were assessed for GAG structure and GlcAT-I expression. Disaccharide analysis showed that 4- and 6-sulfated disaccharides were increased in the lungs and lung fibroblasts obtained from fibrotic rats compared with controls. Fibrotic lung fibroblasts and transforming growth factor-?(1) (TGF-?(1))-treated normal lung fibroblasts expressed increased amounts of hyaluronan and 4- and 6-sulfated chondroitin, and neutralizing anti-TGF-?(1) antibody diminished the same. TGF-?(1) upregulated GlcAT-I and versican expression in lung fibroblasts, and signaling through TGF-? type I receptor/p38 MAPK was required for TGF-?(1)-mediated GlcAT-I and CS-GAG expression in fibroblasts. Our data show for the first time increased expression of CS-GAGs and GlcAT-I in IPF, fibrotic rat lungs, and fibrotic lung fibroblasts. These data suggest that alterations of sulfation isomers of CS/DS and upregulation of GlcAT-I contribute to the pathological PG-GAG accumulation in PF.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1522-1504
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L191-203
pubmed:meshHeading
pubmed-meshheading:21056957-Animals, pubmed-meshheading:21056957-Bleomycin, pubmed-meshheading:21056957-Cells, Cultured, pubmed-meshheading:21056957-Chondroitin Sulfates, pubmed-meshheading:21056957-Dermatan Sulfate, pubmed-meshheading:21056957-Disease Models, Animal, pubmed-meshheading:21056957-Fibroblasts, pubmed-meshheading:21056957-Glucuronosyltransferase, pubmed-meshheading:21056957-Humans, pubmed-meshheading:21056957-Hyaluronic Acid, pubmed-meshheading:21056957-Idiopathic Pulmonary Fibrosis, pubmed-meshheading:21056957-Lung, pubmed-meshheading:21056957-Male, pubmed-meshheading:21056957-Pulmonary Fibrosis, pubmed-meshheading:21056957-RNA, Messenger, pubmed-meshheading:21056957-Rats, pubmed-meshheading:21056957-Rats, Sprague-Dawley, pubmed-meshheading:21056957-Tissue Distribution, pubmed-meshheading:21056957-Transforming Growth Factor beta1, pubmed-meshheading:21056957-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
Increased deposition of chondroitin/dermatan sulfate glycosaminoglycan and upregulation of ?1,3-glucuronosyltransferase I in pulmonary fibrosis.
pubmed:affiliation
McGill Univ., Montréal, QC, Canada. vnar12@yahoo.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't