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Low-dose paclitaxel ameliorates renal fibrosis by suppressing transforming growth factor-1-induced plasminogen activator inhibitor-1 signaling
DC Field | Value | Language |
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dc.contributor.author | Jung, Eun Sook | - |
dc.contributor.author | Lee, Jeonghwan | - |
dc.contributor.author | Heo, Nam Ju | - |
dc.contributor.author | Kim, Sejoong | - |
dc.contributor.author | Kim, Dong Ki | - |
dc.contributor.author | Joo, Kwon Wook | - |
dc.contributor.author | Han, Jin Suk | - |
dc.date.accessioned | 2024-08-08T01:35:56Z | - |
dc.date.available | 2024-08-08T01:35:56Z | - |
dc.date.created | 2018-09-04 | - |
dc.date.created | 2018-09-04 | - |
dc.date.issued | 2016-07 | - |
dc.identifier.citation | Nephrology, Vol.21 No.7, pp.574-582 | - |
dc.identifier.issn | 1320-5358 | - |
dc.identifier.uri | https://hdl.handle.net/10371/206912 | - |
dc.description.abstract | AimTo investigate the effect of microtubule stabilization with low-dose paclitaxel on renal fibrosis, focusing on the transforming growth factor-1 (TGF-1)-induced plasminogen activator inhibitor-1 (PAI-1) signaling cascade. MethodsForty-eight rats were randomly assigned to four groups: sham/vehicle, sham/paclitaxel, unilateral ureteral obstruction (UUO)/vehicle and UUO/paclitaxel. Rats were treated with a 0.3mg/kg intraperitoneal dose of paclitaxel or vehicle twice per week for 14days. Half of the rats in each group were sacrificed respectively on day 7 and 14 after operation. Inner medullar collecting duct (IMCD) cells stimulated with TGF-1 were incubated with 0, 1 and 2 nM paclitaxel for 24 and 72hours. Histological changes were assessed using periodic acid-Schiff and Masson's trichrome. The TGF-1-induced PAI-1 signaling and status of extracellular matrix proteins were evaluated by western blot analysis. ResultsIn the UUO kidneys, paclitaxel significantly attenuated tubular damage and interstitial collagen deposition, as well as -smooth muscle actin (-SMA), TGF-1 and PAI-1 protein expression. Paclitaxel also inhibited the UUO-induced activation of Smad2/3 and c-Jun N-terminal kinase (JNK). However, paclitaxel treatment did not inhibit extracellular signal-regulated kinase 1/2 (ERK1/2) or p38 expression. In TGF-1-treated IMCD cells, treatment with 1 and 2 nM paclitaxel for 72h reduced fibronectin, -SMA and PAI-1 protein expression. Moreover, a 2 nM dose of paclitaxel for 24h significantly inhibited the TGF-1-stimulated activation of Smad2/3, JNK and ERK1/2 in IMCD cells. ConclusionPaclitaxel at low non-cytotoxic doses ameliorates renal fibrosis by inhibiting multiple steps in the TGF-1-induced PAI-1 signaling including Smads and mitogen-activated protein kinases. Summary at a Glance This paper uses a model of experimental renal fibrosis in rats to study the renoprotective effect of low dose paclitaxel, a chemotherapy agent, by inhibiting TGF-b1 and Smad signaling. The study also provides in vitro mechanistic insight into the effects of paciltaxel on TGF-b-stimulated inner medullary collecting ducts. | - |
dc.language | 영어 | - |
dc.publisher | Blackwell Publishing Inc. | - |
dc.title | Low-dose paclitaxel ameliorates renal fibrosis by suppressing transforming growth factor-1-induced plasminogen activator inhibitor-1 signaling | - |
dc.type | Article | - |
dc.identifier.doi | 10.1111/nep.12747 | - |
dc.citation.journaltitle | Nephrology | - |
dc.identifier.wosid | 000379592900004 | - |
dc.identifier.scopusid | 2-s2.0-84976603749 | - |
dc.citation.endpage | 582 | - |
dc.citation.number | 7 | - |
dc.citation.startpage | 574 | - |
dc.citation.volume | 21 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kim, Dong Ki | - |
dc.contributor.affiliatedAuthor | Joo, Kwon Wook | - |
dc.contributor.affiliatedAuthor | Han, Jin Suk | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | TGF-BETA/SMAD ACTIVITY | - |
dc.subject.keywordPlus | BETA | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | KIDNEY | - |
dc.subject.keywordPlus | SMAD | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | ERK | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | OBSTRUCTION | - |
dc.subject.keywordAuthor | fibrosis | - |
dc.subject.keywordAuthor | mitogen-activated protein kinases | - |
dc.subject.keywordAuthor | paclitaxel | - |
dc.subject.keywordAuthor | plasminogen activator inhibitor-1 | - |
dc.subject.keywordAuthor | smad proteins | - |
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