Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-8-23
pubmed:abstractText
We recently showed that suramin treatment prevents the onset of renal fibrosis in a model of obstructive nephropathy induced by unilateral ureteral obstruction (UUO). In this study, we further assessed the effect of delayed administration of suramin on the progression of tubulointerstitial fibrosis. Mice were given a single dose of suramin at 20 mg/kg starting at day 3 of obstruction, and kidneys were harvested after an additional 7 or 14 days of obstruction. Suramin completely blocked further increase in expression of type I collagen and fibronectin and largely suppressed expression of ?-smooth muscle actin (?-SMA) in both treatment groups. UUO injury induced phosphorylation of Smad-3, a key mediator of transforming growth factor-? (TGF-?) signaling, epidermal growth factor receptor, and platelet-derived growth factor receptor after 3 days and further increased at 10 days after UUO injury. When suramin was administered at 3 days after obstruction, phosphorylation of these molecules was not further increased in the obstructed kidney. Suramin treatment also inhibited activation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1 and 2, two signaling pathways associated with renal fibrogenesis. Furthermore, delayed application of suramin suppressed TGF-?1-induced expression of ?-SMA and fibronectin in cultured renal interstitial fibroblasts. These results indicate that administration of suramin is effective in attenuating the progression of renal fibrosis after injury and suggest the potential clinical application of suramin as an antifibrotic treatment in patients with chronic kidney disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
338
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
758-66
pubmed:meshHeading
pubmed-meshheading:21622732-Actins, pubmed-meshheading:21622732-Animals, pubmed-meshheading:21622732-Blotting, Western, pubmed-meshheading:21622732-Cells, Cultured, pubmed-meshheading:21622732-Collagen Type I, pubmed-meshheading:21622732-Disease Progression, pubmed-meshheading:21622732-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:21622732-Fibroblasts, pubmed-meshheading:21622732-Fibronectins, pubmed-meshheading:21622732-Fibrosis, pubmed-meshheading:21622732-Immunohistochemistry, pubmed-meshheading:21622732-Male, pubmed-meshheading:21622732-Mice, pubmed-meshheading:21622732-Mice, Inbred C57BL, pubmed-meshheading:21622732-Nephritis, Interstitial, pubmed-meshheading:21622732-Phosphorylation, pubmed-meshheading:21622732-Receptor, Epidermal Growth Factor, pubmed-meshheading:21622732-Receptors, Platelet-Derived Growth Factor, pubmed-meshheading:21622732-Smad3 Protein, pubmed-meshheading:21622732-Suramin, pubmed-meshheading:21622732-Ureteral Obstruction
pubmed:year
2011
pubmed:articleTitle
Delayed administration of suramin attenuates the progression of renal fibrosis in obstructive nephropathy.
pubmed:affiliation
Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural