{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:49:33Z","timestamp":1791139773091,"version":"4.1.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T00:00:00Z","timestamp":1354147200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1003053","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T22:29:28Z","timestamp":1354228168000},"page":"e1003053","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":99,"title":["Network Analysis of a Pkd1-Mouse Model of Autosomal Dominant Polycystic Kidney Disease Identifies HNF4\u03b1 as a Disease Modifier"],"prefix":"10.1371","volume":"8","author":[{"given":"Luis F.","family":"Menezes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus B.","family":"Piontek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher W.","family":"Krausz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory G.","family":"Germino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,11,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","article-title":"Autosomal dominant polycystic kidney disease","volume":"369","author":"V Torres","year":"2007","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0091-679X(08)94014-0","article-title":"Polycystic kidney disease, cilia, and planar polarity","volume":"94","author":"L Menezes","year":"2009","journal-title":"Methods Cell Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1097\/01.ASN.0000144204.01352.86","article-title":"A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo","volume":"15","author":"K Piontek","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"ref4","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":"K Piontek","year":"2007","journal-title":"Nat Med"},{"key":"ref5","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":"IS Lantinga-van Leeuwen","year":"2007","journal-title":"Hum Mol Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.cub.2007.08.034","article-title":"Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease","volume":"17","author":"JR Davenport","year":"2007","journal-title":"Curr Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nm.2068","article-title":"A mitotic transcriptional switch in polycystic kidney disease","volume":"16","author":"F Verdeguer","year":"2010","journal-title":"Nat Med"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1152\/ajplegacy.1955.181.1.157","article-title":"Maturation of renal function in infant rats","volume":"181","author":"G Falk","year":"1955","journal-title":"Am J Physiol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"F1132","DOI":"10.1152\/ajprenal.00063.2006","article-title":"Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins","volume":"291","author":"G Abuazza","year":"2006","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"F255","DOI":"10.1152\/ajprenal.00400.2006","article-title":"Ontogeny of NHE8 in the rat proximal tubule","volume":"293","author":"A Becker","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"P Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: a network-based approach to human disease","volume":"12","author":"AL Barab\u00e1si","year":"2011","journal-title":"Nat Rev Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2133\/dmpk.23.2","article-title":"Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription","volume":"23","author":"FJ Gonzalez","year":"2008","journal-title":"Drug Metab Pharmacokinet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nm1783","article-title":"A tumor necrosis factor-alpha-mediated pathway promoting autosomal dominant polycystic kidney disease","volume":"14","author":"X Li","year":"2008","journal-title":"Nat Med"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2215\/CJN.04310709","article-title":"The HALT polycystic kidney disease trials: design and implementation","volume":"5","author":"AB Chapman","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nm1004","article-title":"Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease","volume":"10","author":"V Torres","year":"2004","journal-title":"Nat Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1752-0509-1-54","article-title":"Eigengene networks for studying the relationships between co-expression modules","volume":"1","author":"P Langfelder","year":"2007","journal-title":"BMC Syst Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"17973","DOI":"10.1073\/pnas.0605938103","article-title":"Conservation and evolution of gene coexpression networks in human and chimpanzee brains","volume":"103","author":"M Oldham","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s00335-008-9169-y","article-title":"Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract","volume":"20","author":"L Pastorelli","year":"2009","journal-title":"Mamm Genome"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1186\/1471-2164-9-624","article-title":"Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease","volume":"9","author":"P Pandey","year":"2008","journal-title":"BMC Genomics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1752-0509-5-56","article-title":"Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease","volume":"5","author":"P Pandey","year":"2011","journal-title":"BMC Syst Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1172\/JCI34922","article-title":"MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease","volume":"118","author":"S Lee","year":"2008","journal-title":"J Clin Invest"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/hmg\/ddi421","article-title":"Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein expression in murine tissues via alterations in nuclear hormone receptors","volume":"15","author":"E Allen","year":"2006","journal-title":"Hum Mol Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1073\/pnas.1011498108","article-title":"Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis","volume":"108","author":"V Takiar","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","unstructured":"Tanguay RM, Marie L, Markus G, A MG (2011) Hypertyrosinemia. In: Valle, Beaudet, Vogelstein, Kinzler, Antonarakis, <etal>et al<\/etal>.., editors. Scriver&apos;s Online Metabolic and Molecular Bases of Inherited Disease."},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1046\/j.1523-1755.2000.00991.x","article-title":"cAMP stimulates the in vitro proliferation of renal cyst epithelial cells by activating the extracellular signal-regulated kinase pathway","volume":"57","author":"T Yamaguchi","year":"2000","journal-title":"Kidney Int"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"40419","DOI":"10.1074\/jbc.M405079200","article-title":"Calcium restriction allows cAMP activation of the B-Raf\/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype","volume":"279","author":"T Yamaguchi","year":"2004","journal-title":"J Biol Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1203\/00006450-198412000-00021","article-title":"Urinary excretion of l-carnitine and acylcarnitines by patients with disorders of organic acid metabolism: evidence for secondary insufficiency of l-carnitine","volume":"18","author":"RA Chalmers","year":"1984","journal-title":"Pediatr Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/BF00442082","article-title":"Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II), congenital polycystic kidneys, and symmetric warty dysplasia of the cerebral cortex in two newborn brothers. II. Morphology and pathogenesis","volume":"139","author":"N B\u00f6hm","year":"1982","journal-title":"Eur J Pediatr"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ygeno.2004.03.009","article-title":"New insights into ADPKD molecular pathways using combination of SAGE and microarray technologies","volume":"84","author":"H Husson","year":"2004","journal-title":"Genomics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1093\/hmg\/ddp165","article-title":"Systems biology of autosomal dominant polycystic kidney disease (ADPKD): computational identification of gene expression pathways and integrated regulatory networks","volume":"18","author":"X Song","year":"2009","journal-title":"Hum Mol Genet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/1756-0500-1-131","article-title":"Gene expression in early and progression phases of autosomal dominant polycystic kidney disease","volume":"1","author":"W Chen","year":"2008","journal-title":"BMC Res Notes"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1101\/gad.8.20.2466","article-title":"Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos","volume":"8","author":"WS Chen","year":"1994","journal-title":"Genes Dev"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1101\/gad.14.4.464","article-title":"Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha","volume":"14","author":"J Li","year":"2000","journal-title":"Genes Dev"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/ng1175","article-title":"Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis","volume":"34","author":"F Parviz","year":"2003","journal-title":"Nat Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"8419","DOI":"10.1073\/pnas.0600246103","article-title":"Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver","volume":"103","author":"MA Battle","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1053\/j.gastro.2006.01.003","article-title":"Hepatocyte nuclear factor 4alpha is essential for embryonic development of the mouse colon","volume":"130","author":"WD Garrison","year":"2006","journal-title":"Gastroenterology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1128\/MCB.21.4.1393-1403.2001","article-title":"Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis","volume":"21","author":"G Hayhurst","year":"2001","journal-title":"Mol Cell Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/ibd.20413","article-title":"Hepatocyte nuclear factor 4alpha in the intestinal epithelial cells protects against inflammatory bowel disease","volume":"14","author":"SH Ahn","year":"2008","journal-title":"Inflamm Bowel Dis"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"14683","DOI":"10.1074\/jbc.M512636200","article-title":"Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein metabolism","volume":"281","author":"J Rhee","year":"2006","journal-title":"J Biol Chem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1042\/BJ20060659","article-title":"Hepatocyte nuclear factor-4alpha contributes to carbohydrate-induced transcriptional activation of hepatic fatty acid synthase","volume":"399","author":"AW Adamson","year":"2006","journal-title":"Biochem J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.bbamcr.2010.05.008","article-title":"cAMP-mediated regulation of HNF-4alpha depends on the level of coactivator PGC-1alpha","volume":"1803","author":"SN Dankel","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.jhep.2008.04.024","article-title":"Morphogenetic competence of HNF4 alpha-deficient mouse hepatic cells","volume":"49","author":"GP Hayhurst","year":"2008","journal-title":"J Hepatol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1292\/jvms.10-0493","article-title":"Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial transition in developing kidneys of C57BL\/6 mice","volume":"73","author":"T Kanazawa","year":"2011","journal-title":"J Vet Med Sci"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/gene.20047","article-title":"Targeted insertion of an IRES Cre into the Hnf4alpha locus: Cre-mediated recombination in the liver, kidney, and gut epithelium","volume":"39","author":"SD Vincent","year":"2004","journal-title":"Genesis"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"F909","DOI":"10.1152\/ajprenal.00722.2009","article-title":"A metabolomics approach using juvenile cystic mice to identify urinary biomarkers and altered pathways in polycystic kidney disease","volume":"298","author":"SL Taylor","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1440-1797.2011.01532.x","article-title":"Development of a non-targeted metabolomics method to investigate urine in a rat model of polycystic kidney disease","volume":"17","author":"H Abbiss","year":"2012","journal-title":"Nephrology (Carlton)"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.cell.2008.08.021","article-title":"Cancer cell metabolism: Warburg and beyond","volume":"134","author":"PP Hsu","year":"2008","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1755-8417-2-6","article-title":"Emerging evidence of a link between the polycystins and the mTOR pathways","volume":"2","author":"A Boletta","year":"2009","journal-title":"Pathogenetics"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1681\/ASN.2009070718","article-title":"Targeted deletion of Dicer from proximal tubules protects against renal ischemia-reperfusion injury","volume":"21","author":"Q Wei","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"ref51","unstructured":"Rasband WS (1997\u20132011) Imagej, U.S. National Institues of Health, Bethesda, MD, USA."},{"key":"ref52","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: open software development for computational biology and bioinformatics","volume":"5","author":"R Gentleman","year":"2004","journal-title":"Genome Biol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/bioinformatics\/btn224","article-title":"lumi: a pipeline for processing Illumina microarray","volume":"24","author":"P Du","year":"2008","journal-title":"Bioinformatics"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1093\/nar\/gkm1075","article-title":"Model-based variance-stabilizing transformation for Illumina microarray data","volume":"36","author":"S Lin","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"W Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"Article17","DOI":"10.2202\/1544-6115.1128","article-title":"A general framework for weighted gene co-expression network analysis","volume":"4","author":"B Zhang","year":"2005","journal-title":"Stat Appl Genet Mol Biol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1097\/01.ftd.0000179845.53213.39","article-title":"METLIN: a metabolite mass spectral database","volume":"27","author":"CA Smith","year":"2005","journal-title":"Ther Drug Monit"}],"container-title":["PLoS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1003053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T18:13:34Z","timestamp":1643739214000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1003053"}},"subtitle":[],"editor":[{"given":"David R.","family":"Beier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,11,29]]},"references-count":58,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,11,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1003053","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,29]]}}}