{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:03:08Z","timestamp":1787727788361,"version":"build-2784847793"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec>\n<jats:title>Abstract<\/jats:title>\n<jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, caused in the majority of the cases by a mutation in either the <jats:italic>PKD1<\/jats:italic> or the <jats:italic>PKD2<\/jats:italic> gene. ADPKD is characterised by a progressive increase in the number and size of cysts, together with fibrosis and distortion of the renal architecture, over the years. This is accompanied by alterations in a complex network of signalling pathways. However, the underlying molecular mechanisms are not well characterised. Previously, we defined the PKD Signature, a set of genes typically dysregulated in PKD across different disease models from a meta-analysis of expression profiles. Given the importance of transcription factors (TFs) in modulating disease, we focused in this paper on characterising TFs from the PKD Signature. Our results revealed that out of the 1515 genes in the PKD Signature, 92 were TFs with altered expression in PKD, and 32 of those were also implicated in tissue injury\/repair mechanisms. Validating the dysregulation of these TFs by qPCR in independent PKD and injury models largely confirmed these findings. STAT3 and RUNX1 displayed the strongest activation in cystic kidneys, as demonstrated by chromatin immunoprecipitation (ChIP) followed by qPCR. Using immunohistochemistry, we showed a dramatic increase of expression after renal injury in mice and cystic renal tissue of mice and humans. Our results suggest a role for STAT3 and RUNX1 and their downstream targets in the aetiology of ADPKD and indicate that the meta-analysis approach is a viable strategy for new target discovery in PKD.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Key messages<\/jats:title>\n<jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p>We identified a list of transcription factors (TFs) commonly dysregulated in ADPKD.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Out of the 92 TFs identified in the PKD Signature, 35% are also involved in injury\/repair processes.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>STAT3 and RUNX1 are the most significantly dysregulated TFs after injury and during PKD progression.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>STAT3 and RUNX1 activity is increased in cystic compared to non-cystic mouse kidneys.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Increased expression of STAT3 and RUNX1 is observed in the nuclei of renal epithelial cells, also in human ADPKD samples.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00109-019-01852-3","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T14:03:07Z","timestamp":1574776987000},"page":"1643-1656","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Characterisation of transcription factor profiles in polycystic kidney disease (PKD): identification and validation of STAT3 and RUNX1 in the injury\/repair response and PKD progression"],"prefix":"10.1007","volume":"97","author":[{"given":"Chiara","family":"Formica","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tareq","family":"Malas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Balog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"Verburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A. C.","family":"\u2018t Hoen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien J. M.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"issue":"6","key":"1852_CR1","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1172\/JCI72272","volume":"124","author":"PC Harris","year":"2014","unstructured":"Harris PC, Torres VE (2014) Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease. J Clin Invest 124(6):2315\u20132324","journal-title":"J Clin Invest"},{"issue":"12","key":"1852_CR2","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1681\/ASN.2016040425","volume":"27","author":"WN Leonhard","year":"2016","unstructured":"Leonhard WN, Happe H, Peters DJ (2016) Variable cyst development in autosomal dominant polycystic kidney disease: the biologic context. J Am Soc Nephrol 27(12):3530\u20133538","journal-title":"J Am Soc Nephrol"},{"issue":"11","key":"1852_CR3","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1093\/hmg\/ddn045","volume":"17","author":"V Patel","year":"2008","unstructured":"Patel V, Li L, Cobo-Stark P, Shao X, Somlo S, Lin F, Igarashi P (2008) Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia. Hum Mol Genet 17(11):1578\u20131590","journal-title":"Hum Mol Genet"},{"issue":"14","key":"1852_CR4","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1093\/hmg\/ddp190","volume":"18","author":"H Happe","year":"2009","unstructured":"Happe H, Leonhard WN, van der Wal A, van de Water B, Lantinga-van Leeuwen IS, Breuning MH, de Heer E, Peters DJ (2009) Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways. Hum Mol Genet 18(14):2532\u20132542","journal-title":"Hum Mol Genet"},{"issue":"4","key":"1852_CR5","doi-asserted-by":"crossref","first-page":"F806","DOI":"10.1152\/ajprenal.00653.2016","volume":"312","author":"TB Malas","year":"2017","unstructured":"Malas TB, Formica C, Leonhard WN, Rao P, Granchi Z, Roos M, Peters DJ, t Hoen PA (2017) Meta-analysis of polycystic kidney disease expression profiles defines strong involvement of injury repair processes. Am J Physiol Ren Physiol 312(4):F806\u2013F817","journal-title":"Am J Physiol Ren Physiol"},{"issue":"10b","key":"1852_CR6","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1101\/gr.2584104","volume":"14","author":"DN Messina","year":"2004","unstructured":"Messina DN, Glasscock J, Gish W, Lovett M (2004) An ORFeome-based analysis of human transcription factor genes and the construction of a microarray to interrogate their expression. Genome Res 14(10b):2041\u20132047","journal-title":"Genome Res"},{"key":"1852_CR7","doi-asserted-by":"crossref","first-page":"bap004","DOI":"10.1093\/database\/bap004","volume":"2009","author":"RT Moreland","year":"2009","unstructured":"Moreland RT, Ryan JF, Pan C, Baxevanis AD (2009) The homeodomain resource: a comprehensive collection of sequence, structure, interaction, genomic and functional information on the homeodomain protein family. Database (Oxford) 2009:bap004","journal-title":"Database (Oxford)"},{"issue":"19","key":"1852_CR8","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1093\/bioinformatics\/btq466","volume":"26","author":"A Lachmann","year":"2010","unstructured":"Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR, Ma'ayan A (2010) ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26(19):2438\u20132444","journal-title":"Bioinformatics"},{"issue":"10","key":"1852_CR9","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1093\/bioinformatics\/btv770","volume":"32","author":"D Stockel","year":"2016","unstructured":"Stockel D, Kehl T, Trampert P, Schneider L, Backes C, Ludwig N, Gerasch A, Kaufmann M, Gessler M, Graf N, Meese E, Keller A, Lenhof HP (2016) Multi-omics enrichment analysis using the GeneTrail2 web service. Bioinformatics 32(10):1502\u20131508","journal-title":"Bioinformatics"},{"issue":"7","key":"1852_CR10","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"1852_CR11","doi-asserted-by":"crossref","first-page":"D658","DOI":"10.1093\/nar\/gkw983","volume":"45","author":"S Mei","year":"2017","unstructured":"Mei S, Qin Q, Wu Q, Sun H, Zheng R, Zang C, Zhu M, Wu J, Shi X, Taing L, Liu T, Brown M, Meyer CA, Liu XS (2017) Cistrome data browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic Acids Res 45(D1):D658\u2013D662","journal-title":"Nucleic Acids Res"},{"key":"1852_CR12","doi-asserted-by":"publisher","unstructured":"Karolchik D, Hinrichs AS, Kent WJ (2009) The UCSC genome browser. Curr Protoc Bioinformatics Chapter 1:Unit1 4. https:\/\/doi.org\/10.1002\/0471250953.bi0104s28","DOI":"10.1002\/0471250953.bi0104s28"},{"issue":"24","key":"1852_CR13","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1093\/hmg\/ddh336","volume":"13","author":"IS Lantinga-van Leeuwen","year":"2004","unstructured":"Lantinga-van Leeuwen IS, Dauwerse JG, Baelde HJ, Leonhard WN, van de Wal A, Ward CJ, Verbeek S, DeRuiter MC, Breuning MH, de Heer E, Peters DJM (2004) Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum Mol Genet 13(24):3069\u20133077","journal-title":"Hum Mol Genet"},{"issue":"24","key":"1852_CR14","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1093\/hmg\/ddm299","volume":"16","author":"IS Lantinga-van Leeuwen","year":"2007","unstructured":"Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ (2007) Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet 16(24):3188\u20133196","journal-title":"Hum Mol Genet"},{"issue":"1","key":"1852_CR15","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1002\/path.5286","volume":"249","author":"Chiara Formica","year":"2019","unstructured":"Formica C, Happe H, Veraar KAM, Vortkamp A, Scharpfenecker M, McNeill H, Peters DJM (2019) Four-jointed knock-out delays renal failure in an ADPKD model with kidney injury. J Pathol. https:\/\/doi.org\/10.1002\/path.5286","journal-title":"The Journal of Pathology"},{"issue":"1","key":"1852_CR16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nprot.2006.27","volume":"1","author":"JD Nelson","year":"2006","unstructured":"Nelson JD, Denisenko O, Bomsztyk K (2006) Protocol for the fast chromatin immunoprecipitation (ChIP) method. Nat Protoc 1(1):179\u2013185","journal-title":"Nat Protoc"},{"issue":"5","key":"1852_CR17","doi-asserted-by":"crossref","first-page":"F1193","DOI":"10.1152\/ajprenal.00419.2010","volume":"300","author":"WN Leonhard","year":"2011","unstructured":"Leonhard WN, van der Wal A, Novalic Z, Kunnen SJ, Gansevoort RT, Breuning MH, de Heer E, Peters DJ (2011) Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: in vivo evidence from a Pkd1-deletion model. Am J Physiol Ren Physiol 300(5):F1193\u2013F1202","journal-title":"Am J Physiol Ren Physiol"},{"issue":"4","key":"1852_CR18","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/ki.1991.80","volume":"39","author":"M Trudel","year":"1991","unstructured":"Trudel M, Dagati V, Costantini F (1991) C-Myc as an inducer of polycystic kidney-disease in transgenic mice. Kidney Int 39(4):665\u2013671","journal-title":"Kidney Int"},{"issue":"6","key":"1852_CR19","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1681\/ASN.2013080864","volume":"26","author":"WN Leonhard","year":"2015","unstructured":"Leonhard WN, Zandbergen M, Veraar K, van den Berg S, van der Weerd L, Breuning M, de Heer E, Peters DJM (2015) Scattered deletion of PKD1 in kidneys causes a cystic snowball effect and recapitulates polycystic kidney disease. J Am Soc Nephrol 26(6):1322\u20131333","journal-title":"J Am Soc Nephrol"},{"issue":"21","key":"1852_CR20","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1093\/hmg\/ddr338","volume":"20","author":"A Takakura","year":"2011","unstructured":"Takakura A, Nelson EA, Haque N, Humphreys BD, Zandi-Nejad K, Frank DA, Zhou J (2011) Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways. Hum Mol Genet 20(21):4143\u20134154","journal-title":"Hum Mol Genet"},{"issue":"1","key":"1852_CR21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/path.2734","volume":"222","author":"S Hassane","year":"2010","unstructured":"Hassane S, Leonhard WN, van der Wal A, Hawinkels LJ, Lantinga-van Leeuwen IS, ten Dijke P, Breuning MH, de Heer E, Peters DJ (2010) Elevated TGFbeta-Smad signalling in experimental Pkd1 models and human patients with polycystic kidney disease. J Pathol 222(1):21\u201331","journal-title":"J Pathol"},{"issue":"6","key":"1852_CR22","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.kint.2016.03.006","volume":"89","author":"D Lu","year":"2016","unstructured":"Lu D, Rauhauser A, Li B, Ren C, McEnery K, Zhu J, Chaki M, Vadnagara K, Elhadi S, Jetten AM, Igarashi P, Attanasio M (2016) Loss of Glis2\/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease. Kidney Int 89(6):1307\u20131323","journal-title":"Kidney Int"},{"issue":"9","key":"1852_CR23","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1681\/ASN.2004110913","volume":"16","author":"NH Le","year":"2005","unstructured":"Le NH, van der Wal A, van der Bent P, Lantinga-van Leeuwen IS, Breuning MH, van Dam H, de Heer E, Peters DJ (2005) Increased activity of activator protein-1 transcription factor components ATF2, c-Jun, and c-Fos in human and mouse autosomal dominant polycystic kidney disease. J Am Soc Nephrol 16(9):2724\u20132731","journal-title":"J Am Soc Nephrol"},{"issue":"7","key":"1852_CR24","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1172\/JCI64401","volume":"123","author":"X Zhou","year":"2013","unstructured":"Zhou X, Fan LX, Sweeney WE Jr, Denu JM, Avner ED, Li X (2013) Sirtuin 1 inhibition delays cyst formation in autosomal-dominant polycystic kidney disease. J Clin Invest 123(7):3084\u20133098","journal-title":"J Clin Invest"},{"issue":"1","key":"1852_CR25","doi-asserted-by":"crossref","first-page":"F122","DOI":"10.1152\/ajprenal.00352.2017","volume":"314","author":"R Lakhia","year":"2018","unstructured":"Lakhia R, Yheskel M, Flaten A, Quittner-Strom EB, Holland WL, Patel V (2018) PPAR alpha agonist fenofibrate enhances fatty acid beta-oxidation and attenuates polycystic kidney and liver disease in mice. Am J Physiol Ren Physiol 314(1):F122\u2013F131","journal-title":"Am J Physiol Ren Physiol"},{"issue":"8","key":"1852_CR26","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s00109-016-1403-6","volume":"94","author":"LC Ho","year":"2016","unstructured":"Ho LC, Sung JM, Shen YT, Jheng HF, Chen SH, Tsai PJ, Tsai YS (2016) Egr-1 deficiency protects from renal inflammation and fibrosis. J Mol Med (Berl) 94(8):933\u2013942","journal-title":"J Mol Med (Berl)"},{"issue":"9","key":"1852_CR27","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1172\/JCI57582","volume":"121","author":"K Fujiu","year":"2011","unstructured":"Fujiu K, Manabe I, Nagai R (2011) Renal collecting duct epithelial cells regulate inflammation in tubulointerstitial damage in mice. J Clin Invest 121(9):3425\u20133441","journal-title":"J Clin Invest"},{"issue":"5","key":"1852_CR28","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nm.2144","volume":"16","author":"L Yang","year":"2010","unstructured":"Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV (2010) Epithelial cell cycle arrest in G2\/M mediates kidney fibrosis after injury. Nat Med 16(5):535\u2013543, 531p following 143","journal-title":"Nat Med"},{"key":"1852_CR29","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/978-3-319-51436-9_12","volume":"60","author":"CJ Song","year":"2017","unstructured":"Song CJ, Zimmerman KA, Henke SJ, Yoder BK (2017) Inflammation and fibrosis in polycystic kidney disease. Results Probl Cell Differ 60:323\u2013344","journal-title":"Results Probl Cell Differ"},{"issue":"7","key":"1852_CR30","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1681\/ASN.2005121298","volume":"17","author":"MB Shannon","year":"2006","unstructured":"Shannon MB, Patton BL, Harvey SJ, Miner JH (2006) A hypomorphic mutation in the mouse laminin alpha5 gene causes polycystic kidney disease. J Am Soc Nephrol 17(7):1913\u20131922","journal-title":"J Am Soc Nephrol"},{"issue":"4","key":"1852_CR31","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1681\/ASN.2013111179","volume":"26","author":"K Lee","year":"2015","unstructured":"Lee K, Boctor S, Barisoni LM, Gusella GL (2015) Inactivation of integrin-beta1 prevents the development of polycystic kidney disease after the loss of polycystin-1. J Am Soc Nephrol 26(4):888\u2013895","journal-title":"J Am Soc Nephrol"},{"issue":"4","key":"1852_CR32","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1681\/ASN.2006121378","volume":"19","author":"YX Tao","year":"2008","unstructured":"Tao YX, Zafar I, Kim J, Schrier RW, Edelstein CL (2008) Caspase-3 gene deletion prolongs survival in polycystic kidney disease. J Am Soc Nephrol 19(4):749\u2013755","journal-title":"J Am Soc Nephrol"},{"issue":"11","key":"1852_CR33","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41581-018-0051-1","volume":"14","author":"V Padovano","year":"2018","unstructured":"Padovano V, Podrini C, Boletta A, Caplan MJ (2018) Metabolism and mitochondria in polycystic kidney disease research and therapy. Nat Rev Nephrol 14(11):678\u2013687","journal-title":"Nat Rev Nephrol"},{"issue":"3","key":"1852_CR34","first-page":"619","volume":"41","author":"M Merta","year":"1997","unstructured":"Merta M, Tesar V, Zima T, Jirsa M, Rysava R, Zabka J (1997) Cytokine profile in autosomal dominant polycystic kidney disease. Biochem Mol Biol Int 41(3):619\u2013624","journal-title":"Biochem Mol Biol Int"},{"issue":"4","key":"1852_CR35","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1111\/j.1523-1755.2005.00589.x","volume":"68","author":"KD Stringer","year":"2005","unstructured":"Stringer KD, Komers R, Osman SA, Oyama TT, Lindsley JN, Anderson S (2005) Gender hormones and the progression of experimental polycystic kidney disease. Kidney Int 68(4):1729\u20131739","journal-title":"Kidney Int"},{"issue":"19","key":"1852_CR36","doi-asserted-by":"crossref","first-page":"7985","DOI":"10.1073\/pnas.1103816108","volume":"108","author":"JJ Talbot","year":"2011","unstructured":"Talbot JJ, Shillingford JM, Vasanth S, Doerr N, Mukherjee S, Kinter MT, Watnick T, Weimbs T (2011) Polycystin-1 regulates STAT activity by a dual mechanism. Proc Natl Acad Sci U S A 108(19):7985\u20137990","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"19","key":"1852_CR37","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1038\/emboj.2012.231","volume":"31","author":"BG Weijts","year":"2012","unstructured":"Weijts BG, Bakker WJ, Cornelissen PW, Liang KH, Schaftenaar FH, Westendorp B, de Wolf CA, Paciejewska M, Scheele CL, Kent L, Leone G, Schulte-Merker S, de Bruin A (2012) E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1. EMBO J 31(19):3871\u20133884","journal-title":"EMBO J"},{"issue":"14","key":"1852_CR38","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1101\/gad.184911.111","volume":"26","author":"LA Carvajal","year":"2012","unstructured":"Carvajal LA, Hamard P-J, Tonnessen C, Manfredi JJ (2012) E2F7, a novel target, is up-regulated by p53 and mediates DNA damage-dependent transcriptional repression. Genes Dev 26(14):1533\u20131545","journal-title":"Genes Dev"},{"issue":"30","key":"1852_CR39","doi-asserted-by":"crossref","first-page":"26267","DOI":"10.1074\/jbc.R111.252569","volume":"286","author":"S Iyengar","year":"2011","unstructured":"Iyengar S, Farnham PJ (2011) KAP1 protein: an enigmatic master regulator of the genome. J Biol Chem 286(30):26267\u201326276","journal-title":"J Biol Chem"},{"issue":"3","key":"1852_CR40","doi-asserted-by":"crossref","first-page":"255","DOI":"10.4161\/cc.6.3.3799","volume":"6","author":"DK Carroll","year":"2007","unstructured":"Carroll DK, Brugge JS, Attardi LD (2007) p63, cell adhesion and survival. Cell cycle (Georgetown, Tex) 6(3):255\u2013261","journal-title":"Cell cycle (Georgetown, Tex)"},{"issue":"6","key":"1852_CR41","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1159\/000480216","volume":"42","author":"J Liu","year":"2017","unstructured":"Liu J, Zhong Y, Liu G, Zhang X, Xiao B, Huang S, Liu H, He L (2017) Role of Stat3 signaling in control of EMT of tubular epithelial cells during renal fibrosis. Cell Physiol Biochem 42(6):2552\u20132558","journal-title":"Cell Physiol Biochem"},{"issue":"6","key":"1852_CR42","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1681\/ASN.2007070744","volume":"19","author":"Y Nechemia-Arbely","year":"2008","unstructured":"Nechemia-Arbely Y, Barkan D, Pizov G, Shriki A, Rose-John S, Galun E, Axelrod JH (2008) IL-6\/IL-6R axis plays a critical role in acute kidney injury. J Am Soc Nephrol 19(6):1106\u20131115","journal-title":"J Am Soc Nephrol"},{"issue":"41","key":"1852_CR43","doi-asserted-by":"crossref","first-page":"30884","DOI":"10.1074\/jbc.M604772200","volume":"281","author":"Z Xiao","year":"2006","unstructured":"Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer BS, Guo D, Dallas SL, Maser R, Calvet JP, Bonewald L, Quarles LD (2006) Cilia-like structures and polycystin-1 in osteoblasts\/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem 281(41):30884\u201330895","journal-title":"J Biol Chem"},{"key":"1852_CR44","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/1471-213X-7-84","volume":"7","author":"A Pozner","year":"2007","unstructured":"Pozner A, Lotem J, Xiao C, Goldenberg D, Brenner O, Negreanu V, Levanon D, Groner Y (2007) Developmentally regulated promoter-switch transcriptionally controls Runx1 function during embryonic hematopoiesis. BMC Dev Biol 7:84","journal-title":"BMC Dev Biol"},{"issue":"3","key":"1852_CR45","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1182\/blood-2007-08-109702","volume":"111","author":"L Zhang","year":"2008","unstructured":"Zhang L, Fried FB, Guo H, Friedman AD (2008) Cyclin-dependent kinase phosphorylation of RUNX1\/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation. Blood 111(3):1193\u20131200","journal-title":"Blood"},{"issue":"2","key":"1852_CR46","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1165\/rcmb.2016-0319OC","volume":"57","author":"X Tang","year":"2017","unstructured":"Tang X, Sun L, Jin X, Chen Y, Zhu H, Liang Y, Wu Q, Han X, Liang J, Liu X, Liang Z, Wang G, Luo F (2017) Runt-related transcription factor 1 regulates LPS-induced acute lung injury via NF-kappaB signaling. Am J Respir Cell Mol Biol 57(2):174\u2013183","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"8","key":"1852_CR47","doi-asserted-by":"crossref","first-page":"e1005457","DOI":"10.1371\/journal.pgen.1005457","volume":"11","author":"KB Umansky","year":"2015","unstructured":"Umansky KB, Gruenbaum-Cohen Y, Tsoory M, Feldmesser E, Goldenberg D, Brenner O, Groner Y (2015) Runx1 transcription factor is required for myoblasts proliferation during muscle regeneration. PLoS Genet 11(8):e1005457","journal-title":"PLoS Genet"},{"issue":"3","key":"1852_CR48","doi-asserted-by":"crossref","first-page":"e59250","DOI":"10.1371\/journal.pone.0059250","volume":"8","author":"TT Logan","year":"2013","unstructured":"Logan TT, Villapol S, Symes AJ (2013) TGF-beta superfamily gene expression and induction of the Runx1 transcription factor in adult neurogenic regions after brain injury. PLoS One 8(3):e59250","journal-title":"PLoS One"},{"key":"1852_CR49","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ebiom.2018.04.023","volume":"31","author":"T Zhou","year":"2018","unstructured":"Zhou T, Luo M, Cai W, Zhou S, Feng D, Xu C, Wang H (2018) Runt-related transcription factor 1 (RUNX1) promotes TGF-beta-induced renal tubular epithelial-to-mesenchymal transition (EMT) and renal fibrosis through the PI3K subunit p110delta. EBioMedicine 31:217\u2013225","journal-title":"EBioMedicine"},{"issue":"5","key":"1852_CR50","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1080\/1354750X.2018.1443509","volume":"23","author":"G Zhang","year":"2018","unstructured":"Zhang G, Han G, Zhang X, Yu Q, Li Z, Li Z, Li J (2018) Long non-coding RNA FENDRR reduces prostate cancer malignancy by competitively binding miR-18a-5p with RUNX1. Biomarkers 23(5):435\u2013445","journal-title":"Biomarkers"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-019-01852-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00109-019-01852-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-019-01852-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:21:20Z","timestamp":1606263680000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00109-019-01852-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,26]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1852"],"URL":"https:\/\/doi.org\/10.1007\/s00109-019-01852-3","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,26]]},"assertion":[{"value":"16 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}