Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 하헌주 | * |
dc.date.accessioned | 2018-05-18T08:15:15Z | - |
dc.date.available | 2018-05-18T08:15:15Z | - |
dc.date.issued | 2005 | * |
dc.identifier.issn | 1046-6673 | * |
dc.identifier.other | OAK-2604 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/243195 | - |
dc.description.abstract | Epithelial-mesenchymal transition (EMT) plays an important role in renal tubulointerstitial fibrosis and TGF-β1 is the key inducer of EMT. Phosphorylation of Smad proteins and/or mitogen-activated protein kinases (MAPK) is required for TGF-β1-induced EMT. Because reactive oxygen species (ROS) are involved in TGF-β1 signaling and are upstream signaling molecules to MAPK, this study examined the role of ROS in TGF-β1-induced MAPK activation and EMT in rat proximal tubular epithelial cells. Growth-arrested and synchronized NRK-52E cells were stimulated with TGF-β1 (0.2 to 20 ng/ml) or H 2O 2 (1 to 500 μM) in the presence or absence of antioxidants (N-acetylcysteine or catalase), inhibitors of NADPH oxidase (diphenyleneiodonium and apocynin), mitochondrial electron transfer chain subunit I (rotenone), and MAPK (PD 98059, an MEK [MAP kinase/ERK kinase] inhibitor, or p38 MAPK inhibitor) for up to 96 h. TGF-β1 increased dichlorofluorescein-sensitive cellular ROS, phosphorylated Smad 2, p38 MAPK, extracellular signal-regulated kinases (ERK)1/2, α-smooth muscle actin (α-SMA) expression, and fibronectin secretion and decreased E-cadherin expression. Antioxidants effectively inhibited TGF-β1-induced cellular ROS, phosphorylation of Smad 2, p38 MAPK, and ERK, and EMT. H 2O 2 reproduced all of the effects of TGF-β1 with the exception of Smad 2 phosphorylation. Chemical inhibition of ERK but not p38 MAPK inhibited TGF-β1-induced Smad 2 phosphorylation, and both MAPK inhibitors inhibited TGF-β1- and H 2O 2-induced EMT. Diphenyleneiodonium, apocynin, and rotenone also significantly inhibited TGF-β1-induced ROS. Thus, this data suggest that ROS play an important role in TGF-β1-induced EMT primarily through activation of MAPK and subsequently through ERK-directed activation of Smad pathway in proximal tubular epithelial cells. Copyright © 2005 by the American Society of Nephrology. | * |
dc.language | English | * |
dc.title | Role of reactive oxygen species in TGF-β1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells | * |
dc.type | Article | * |
dc.relation.issue | 3 | * |
dc.relation.volume | 16 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 667 | * |
dc.relation.lastpage | 675 | * |
dc.relation.journaltitle | Journal of the American Society of Nephrology | * |
dc.identifier.doi | 10.1681/ASN.2004050425 | * |
dc.identifier.wosid | WOS:000227372000015 | * |
dc.identifier.scopusid | 2-s2.0-20544437490 | * |
dc.author.google | Rhyu D.Y. | * |
dc.author.google | Yang Y. | * |
dc.author.google | Ha H. | * |
dc.author.google | Lee G.T. | * |
dc.author.google | Song J.S. | * |
dc.author.google | Uh S.-T. | * |
dc.author.google | Lee H.B. | * |
dc.contributor.scopusid | 하헌주(7202277106) | * |
dc.date.modifydate | 20240422113229 | * |