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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-26
pubmed:abstractText
The inhibitory effects of recombinant human erythropoietin (rhEPO) were examined against (1) the progression of renal fibrosis in mice with complete unilateral ureteral obstruction and (2) the TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) in MDCK cells. Unilateral ureteral obstruction was induced in BALB/c mice and rhEPO (100 or 1000 U/kg, intraperitoneally, every other day) or vehicle was administered from day 3 to day 14. Immunoblotting and immunohistochemistry revealed increased expressions of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-beta1 and alpha-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-beta1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-beta1 and rhEPO for another 48 h. Increased expressions of alpha-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-beta1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-beta1 increased phosphorylated Smad-2 expression in MDCK cells, which was decreased by rhEPO co-treatment. In conclusion, rhEPO treatment inhibits the progression of renal fibrosis in obstructed kidney and attenuates the TGF-beta1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-beta1-induced EMT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1497-507
pubmed:meshHeading
pubmed-meshheading:17389738-Actins, pubmed-meshheading:17389738-Animals, pubmed-meshheading:17389738-Cells, Cultured, pubmed-meshheading:17389738-Disease Progression, pubmed-meshheading:17389738-Dogs, pubmed-meshheading:17389738-Epithelial Cells, pubmed-meshheading:17389738-Erythropoietin, pubmed-meshheading:17389738-Fibronectins, pubmed-meshheading:17389738-Fibrosis, pubmed-meshheading:17389738-Humans, pubmed-meshheading:17389738-Kidney, pubmed-meshheading:17389738-Kidney Diseases, pubmed-meshheading:17389738-Male, pubmed-meshheading:17389738-Mesoderm, pubmed-meshheading:17389738-Mice, pubmed-meshheading:17389738-Mice, Inbred BALB C, pubmed-meshheading:17389738-Recombinant Proteins, pubmed-meshheading:17389738-Transforming Growth Factor beta1, pubmed-meshheading:17389738-Ureteral Obstruction
pubmed:year
2007
pubmed:articleTitle
Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition.
pubmed:affiliation
Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies