{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:18:54Z","timestamp":1791778734595,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"DOI":"10.1093\/hmg\/ddr338","type":"journal-article","created":{"date-parts":[[2011,8,5]],"date-time":"2011-08-05T23:49:53Z","timestamp":1312588193000},"page":"4143-4154","source":"Crossref","is-referenced-by-count":126,"title":["Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways"],"prefix":"10.1093","volume":"20","author":[{"given":"Ayumi","family":"Takakura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Haque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Humphreys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kambiz","family":"Zandi-Nejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,5]]},"reference":[{"key":"key\n\t\t\t\t20170522134032_DDR338C1","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1056\/NEJM199307293290508","article-title":"Autosomal dominant polycystic kidney disease","volume":"329","author":"Gabow","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"key\n\t\t\t\t20170522134032_DDR338C2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1159\/000421651","article-title":"Genetic heterogeneity of polycystic kidney disease in Europe","volume":"97","author":"Peters","year":"1992","journal-title":"Contrib. Nephrol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C3","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1681\/ASN.2007101139","article-title":"Pkd1 inactivation induced in adulthood produces focal cystic disease","volume":"19","author":"Takakura","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C4","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/nm1675","article-title":"A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1","volume":"13","author":"Piontek","year":"2007","journal-title":"Nat. Med."},{"key":"key\n\t\t\t\t20170522134032_DDR338C5","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1093\/hmg\/ddm299","article-title":"Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice","volume":"16","author":"Lantinga-van Leeuwen","year":"2007","journal-title":"Hum. Mol. Genet."},{"issue":"Suppl. 1","key":"key\n\t\t\t\t20170522134032_DDR338C6","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1097\/01.ASN.0000067652.51441.21","article-title":"Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure","volume":"14","author":"Bonventre","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C7","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1093\/hmg\/ddp147","article-title":"Renal injury is a third hit promoting rapid development of adult polycystic kidney disease","volume":"18","author":"Takakura","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522134032_DDR338C8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1023\/A:1006974330613","article-title":"Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy","volume":"196","author":"Ghatpande","year":"1999","journal-title":"Mol. Cell. Biochem."},{"key":"key\n\t\t\t\t20170522134032_DDR338C9","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1161\/01.CIR.104.3.325","article-title":"JAK\/STAT signaling is associated with cardiac dysfunction during ischemia and reperfusion","volume":"104","author":"Mascareno","year":"2001","journal-title":"Circulation"},{"key":"key\n\t\t\t\t20170522134032_DDR338C10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1242\/dev.00202","article-title":"Localized JAK\/STAT signaling is required for oriented cell rearrangement in a tubular epithelium","volume":"130","author":"Johansen","year":"2003","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522134032_DDR338C11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nrg977","article-title":"The evolution of signalling pathways in animal development","volume":"4","author":"Pires-daSilva","year":"2003","journal-title":"Nat. Rev. Genet."},{"key":"key\n\t\t\t\t20170522134032_DDR338C12","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1534-5807(02)00412-4","article-title":"A gradient of JAK pathway activity patterns the anterior-posterior axis of the follicular epithelium","volume":"4","author":"Xi","year":"2003","journal-title":"Dev. Cell"},{"key":"key\n\t\t\t\t20170522134032_DDR338C13","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1126\/science.1071545","article-title":"A road map for those who don't know JAK-STAT","volume":"296","author":"Aaronson","year":"2002","journal-title":"Science"},{"key":"key\n\t\t\t\t20170522134032_DDR338C14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/sj.onc.1205004","article-title":"Requirement of Stat3 signaling for HGF\/SF-Met mediated tumorigenesis","volume":"21","author":"Zhang","year":"2002","journal-title":"Oncogene"},{"key":"key\n\t\t\t\t20170522134032_DDR338C15","first-page":"S93","article-title":"Mechanisms of progression in autosomal dominant polycystic kidney disease","volume":"63","author":"Grantham","year":"1997","journal-title":"Kidney Int. Suppl."},{"key":"key\n\t\t\t\t20170522134032_DDR338C16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000059888","article-title":"Inflammatory cytokine profile in autosomal dominant polycystic kidney disease","volume":"122","author":"Merta","year":"1997","journal-title":"Contrib. Nephrol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C17","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1172\/JCI41531","article-title":"Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease","volume":"120","author":"Qin","year":"2010","journal-title":"J. Clin. Invest."},{"key":"key\n\t\t\t\t20170522134032_DDR338C18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0960-9822(99)00268-7","article-title":"Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR","volume":"10","author":"Yokogami","year":"2000","journal-title":"Curr. Biol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C19","doi-asserted-by":"crossref","first-page":"5466","DOI":"10.1073\/pnas.0509694103","article-title":"The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease","volume":"103","author":"Shillingford","year":"2006","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20170522134032_DDR338C20","doi-asserted-by":"crossref","first-page":"F693","DOI":"10.1152\/ajprenal.2001.281.4.F693","article-title":"Rapamycin impairs recovery from acute renal failure: role of cell-cycle arrest and apoptosis of tubular cells","volume":"281","author":"Lieberthal","year":"2001","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C21","first-page":"3351","article-title":"Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma","volume":"62","author":"Masuda","year":"2002","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170522134032_DDR338C22","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/S0022-5347(05)64741-6","article-title":"Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome","volume":"168","author":"Horiguchi","year":"2002","journal-title":"J. Urol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C23","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1097\/00007890-200205270-00008","article-title":"Rapamycin blocks tumor progression: unlinking immunosuppression from antitumor efficacy","volume":"73","author":"Luan","year":"2002","journal-title":"Transplantation"},{"key":"key\n\t\t\t\t20170522134032_DDR338C24","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1152\/ajprenal.00419.2010","article-title":"Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: in vivo evidence from a Pkd1-deletion model","volume":"300","author":"Leonhard","year":"2011","journal-title":"Am. J. Physiol. Renal Physiol"},{"key":"key\n\t\t\t\t20170522134032_DDR338C25","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.matbio.2008.05.002","article-title":"Col2-Cre recombinase is co-expressed with endogenous type II collagen in embryonic renal epithelium and drives development of polycystic kidney disease following inactivation of ciliary genes","volume":"27","author":"Kolpakova-Hart","year":"2008","journal-title":"Matrix Biol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C26","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1056\/NEJMoa1003491","article-title":"Everolimus in patients with autosomal dominant polycystic kidney disease","volume":"363","author":"Walz","year":"2010","journal-title":"N. Engl. J. Med"},{"key":"key\n\t\t\t\t20170522134032_DDR338C27","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1056\/NEJMoa0907419","article-title":"Sirolimus and kidney growth in autosomal dominant polycystic kidney disease","volume":"363","author":"Serra","year":"2010","journal-title":"N. Engl. J. Med"},{"key":"key\n\t\t\t\t20170522134032_DDR338C28","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1111\/j.1600-6143.2010.03152.x","article-title":"Therapeutic mTOR inhibition in autosomal dominant polycystic kidney disease: what is the appropriate serum level?","volume":"10","author":"Canaud","year":"2010","journal-title":"Am. J. Transplant."},{"key":"key\n\t\t\t\t20170522134032_DDR338C29","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.2215\/CJN.01360210","article-title":"Prospects for mTOR inhibitor use in patients with polycystic kidney disease and hamartomatous diseases","volume":"5","author":"Torres","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"key\n\t\t\t\t20170522134032_DDR338C30","doi-asserted-by":"crossref","first-page":"5095","DOI":"10.1182\/blood-2007-12-129718","article-title":"Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3","volume":"112","author":"Nelson","year":"2008","journal-title":"Blood"},{"key":"key\n\t\t\t\t20170522134032_DDR338C31","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.stem.2008.01.014","article-title":"Intrinsic epithelial cells repair the kidney after injury","volume":"2","author":"Humphreys","year":"2008","journal-title":"Cell Stem Cell"},{"key":"key\n\t\t\t\t20170522134032_DDR338C32","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1128\/AAC.40.7.1623","article-title":"Plasma pyrimethamine concentrations during long-term treatment for cerebral toxoplasmosis in patients with AIDS","volume":"40","author":"Klinker","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"key\n\t\t\t\t20170522134032_DDR338C33","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1158\/0008-5472.CAN-08-0222","article-title":"Pyrimethamine induces apoptosis of melanoma cells via a caspase and cathepsin double-edged mechanism","volume":"68","author":"Giammarioli","year":"2008","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170522134032_DDR338C34","doi-asserted-by":"crossref","first-page":"7391","DOI":"10.1073\/pnas.0609757104","article-title":"Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity","volume":"104","author":"Siddiquee","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20170522134032_DDR338C35","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1093\/hmg\/ddp190","article-title":"Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways","volume":"18","author":"Happe","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522134032_DDR338C36","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.virusres.2010.08.018","article-title":"Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1 replication","volume":"153","author":"Oguariri","year":"2010","journal-title":"Virus Res."},{"key":"key\n\t\t\t\t20170522134032_DDR338C37","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.bbrc.2007.09.049","article-title":"Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells","volume":"363","author":"Fuke","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"key\n\t\t\t\t20170522134032_DDR338C38","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/ki.2010.154","article-title":"A novel STAT3 inhibitor, S3I-201, attenuates renal interstitial fibroblast activation and interstitial fibrosis in obstructive nephropathy","volume":"78","author":"Pang","year":"2010","journal-title":"Kidney Int."},{"key":"key\n\t\t\t\t20170522134032_DDR338C39","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0092-8674(02)00716-X","article-title":"PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2","volume":"109","author":"Bhunia","year":"2002","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170522134032_DDR338C40","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0092-8674(00)81289-1","article-title":"Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease","volume":"84","author":"Durbin","year":"1996","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170522134032_DDR338C41","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0092-8674(00)81288-X","article-title":"Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway","volume":"84","author":"Meraz","year":"1996","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170522134032_DDR338C42","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1101\/gad.13.11.1361","article-title":"FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway","volume":"13","author":"Sahni","year":"1999","journal-title":"Genes Dev."},{"key":"key\n\t\t\t\t20170522134032_DDR338C43","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1093\/hmg\/10.21.2385","article-title":"Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects","volume":"10","author":"Lu","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522134032_DDR338C44","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1681\/ASN.2005080830","article-title":"Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction","volume":"17","author":"Nauli","year":"2006","journal-title":"J. Am. Soc. Nephrol."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/20\/21\/4143\/17252793\/ddr338.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T16:55:04Z","timestamp":1560444904000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article-lookup\/doi\/10.1093\/hmg\/ddr338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,5]]},"references-count":44,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2011,8,5]]},"published-print":{"date-parts":[[2011,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddr338","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13296967.14657069","asserted-by":"object"}]},"ISSN":["1460-2083","0964-6906"],"issn-type":[{"value":"1460-2083","type":"electronic"},{"value":"0964-6906","type":"print"}],"subject":[],"published":{"date-parts":[[2011,8,5]]}}}