Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/95840
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dc.contributor.author許美鈴zh_TW
dc.contributor.authorSheu, Meei-Lingzh_TW
dc.contributor.authorShen, Chin-Changzh_TW
dc.contributor.authorJheng, Jia-Rongzh_TW
dc.contributor.authorChiang, Chih-Kangzh_TW
dc.date2017-03-07-
dc.date.accessioned2018-10-26T07:02:37Z-
dc.date.available2018-10-26T07:02:37Z-
dc.identifier.urihttp://hdl.handle.net/11455/95840-
dc.description.abstractExcessive deposition of extracellular matrix (ECM) in the glomerulus contributed by mesangial cells is the hallmark of diabetic nephropathy, eventually leading to glomerulosclerosis. In this study, we examined the regulatory signals involved in the high glucose (HG)-induced overproduction of ECM in rat mesangial cells (RMCs). We disclosed excessive fibronectin and collagen IV production, tyrosine phosphorylation of signal transducer and activator of transcription 1 and 3 (STAT1/3), and up-regulation of suppressor of cytokine signaling-3 (SOCS-3) expression in HG-treated RMCs. STAT1/STAT3 binding element was essential for SOCS-3 promoter activity stimulated by HG. HG was capable of promoting the specific DNA binding activities to an oligonucleotide probe containing the SOCS-3 sequence. The selective phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and dominant negative p85 vector (DNΔp85) transfection effectively abolished these HG-induced responses. Moreover, HG markedly increased the cyclin kinase inhibitor p27Kip1 protein expression, which could be inhibited by LY294002 or transfection of DNΔp85. Taken together, these results suggest that HG-induced SOCS-3 upregulation depends upon the presence of STAT-binding element in the SOCS-3 promoter, which is specifically activated by STAT1/3. The PI3K/STAT1/3 signaling pathway mediated HG-triggered ECM accumulation and SOCS-3 upregulation in RMCs.zh_TW
dc.language.isoen_USzh_TW
dc.publisherONCOTARGETzh_TW
dc.relationOncotarget, Volume 8, Issue 10, Page(s) 16925-16938.zh_TW
dc.subjectextracellular matrixzh_TW
dc.subjecthigh glucosezh_TW
dc.subjectmesangial cellzh_TW
dc.subjectphosphoinositide 3-kinasezh_TW
dc.subjectsignal transductionzh_TW
dc.subjectAnimalszh_TW
dc.subjectBase Sequencezh_TW
dc.subjectCell Linezh_TW
dc.subjectCells, Culturedzh_TW
dc.subjectDose-Response Relationship, Drugzh_TW
dc.subjectEnzyme Activationzh_TW
dc.subjectExtracellular Matrixzh_TW
dc.subjectGlucosezh_TW
dc.subjectImmunoblottingzh_TW
dc.subjectMalezh_TW
dc.subjectMesangial Cellszh_TW
dc.subjectPhosphatidylinositol 3-Kinaseszh_TW
dc.subjectPromoter Regions, Geneticzh_TW
dc.subjectProtein Bindingzh_TW
dc.subjectRats, Sprague-Dawleyzh_TW
dc.subjectSTAT1 Transcription Factorzh_TW
dc.subjectSTAT3 Transcription Factorzh_TW
dc.subjectSignal Transductionzh_TW
dc.subjectSuppressor of Cytokine Signaling 3 Proteinzh_TW
dc.subjectTime Factorszh_TW
dc.titleActivation of PI3K in response to high glucose leads to regulation of SOCS-3 and STAT1/3 signals and induction of glomerular mesangial extracellular matrix formationzh_TW
dc.typeJournal Articlezh_TW
dc.identifier.doi10.18632/oncotarget.14808zh_TW
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.cerifentitytypePublications-
item.fulltextwith fulltext-
item.languageiso639-1en_US-
item.grantfulltextrestricted-
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