Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 강덕희 | - |
dc.date.accessioned | 2016-08-27T02:08:12Z | - |
dc.date.available | 2016-08-27T02:08:12Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 0085-2538 | - |
dc.identifier.other | OAK-2258 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/215831 | - |
dc.description.abstract | Background. Angiogenesis has a key role in numerous disease processes. One of the most important angiogenic factors is vascular endothelial growth factor (VEGF-A), whereas thrombospondin-1 (TSP-1) is a major antiangiogenic factor. Recent studies have shown that VEGF-A as well as TSP-1 is regulated by transforming growth factor-beta1 (TGF-beta1), but the mechanism remains unclear. Methods. We examined the role of TGF-beta1 and its signaling pathways in mediating expression of these two molecules. Rat proximal tubular cells (NRK52E) were stimulated with TGF-beta1 to induce VEGF-A and TSP-1 synthesis. To clarify roles of receptor-activated Smads (R-Smads), we blocked Smad signaling using overexpression of the inhibitory Smad, Smad7, and by using fibroblasts from wild-type or knockout mice. To confirm the antiantigenic role of Smads, soluble Flt-1 regulation in response to TGF-beta1 was also examined. In addition, the effect of conditioned media from NRK52E and Smad knockout cells was examined on endothelial cell proliferation. Results. Induction of VEGF-A and TSP-1 by TGF-beta1 in NRK52E cells was associated with activation of pathway-restricted R-Smads (Smad2 and 3) and blocking these Smads by overexpression of Smad7 blocked their induction. By using of Smad knockout cells, Smad3 was shown to have a key role in the stimulation of VEGF-A expression whereas Smad2 was critical for TSP-1 expression. Consistent with the hypothesis that Smad2 has an antiangiogenic function, we also demonstrated that Smad2, but not Smad3, mediated the expression of VEGF-A antagonist, soluble VEGF-A receptor sFlt-1, in response to TGF-beta1. Conditioned media from NRK52E, which was stimulated by TGF-beta1 for 24 hours, did not induce endothelial cell proliferation. However, conditioned media from Smad2 knockout induced endothelial cell proliferation, whereas endothelial cell proliferation was inhibited by Smad3 knockout-derived conditioned media. Conclusion. R-Smads have distinct roles in mediating the expression of pro- and antiangiogenic growth factors in response to TGF-beta1. | - |
dc.language | English | - |
dc.publisher | BLACKWELL PUBLISHING INC | - |
dc.subject | VEGF | - |
dc.subject | TSP-1 | - |
dc.subject | sFlt-1 | - |
dc.subject | Smad KO cell | - |
dc.subject | endothelial cell proliferation | - |
dc.title | TGF-beta induces proangiogenic and antiangiogenic factors via parallel but distinct Smad pathways | - |
dc.type | Article | - |
dc.relation.issue | 2 | - |
dc.relation.volume | 66 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 605 | - |
dc.relation.lastpage | 613 | - |
dc.relation.journaltitle | KIDNEY INTERNATIONAL | - |
dc.identifier.doi | 10.1111/j.1523-1755.2004.00780.x | - |
dc.identifier.wosid | WOS:000222578400022 | - |
dc.author.google | Nakagawa, T | - |
dc.author.google | Li, JH | - |
dc.author.google | Garcia, G | - |
dc.author.google | Mu, W | - |
dc.author.google | Piek, E | - |
dc.author.google | Bottinger, EP | - |
dc.author.google | Chen, Y | - |
dc.author.google | Zhu, HJ | - |
dc.author.google | Kang, DH | - |
dc.author.google | Schreiner, GF | - |
dc.author.google | Lan, HY | - |
dc.author.google | Johnson, RJ | - |
dc.contributor.scopusid | 강덕희(17233695600) | - |
dc.date.modifydate | 20230210140157 | - |