{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:14:52Z","timestamp":1794003292729,"version":"4.8.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK083525"],"award-info":[{"award-number":["DK083525"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and is characterized by progressive growth of fluid-filled cysts. Growth factors binding to receptor tyrosine kinases (RTKs) stimulate cell proliferation and cyst growth in PKD. Nintedanib, a triple RTK inhibitor, targets the vascular endothelial growth-factor receptor (VEGFR), platelet-derived growth-factor receptor (PDGFR), and fibroblast growth-factor receptor (FGFR), and is an approved drug for the treatment of non-small-cell lung carcinoma and idiopathic lung fibrosis. To determine if RTK inhibition using nintedanib can slow ADPKD progression, we tested its effect on human ADPKD renal cyst epithelial cells and myofibroblasts in vitro, and on\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>f\/f<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Cre<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>RC\/RC<\/jats:italic>\n                    <\/jats:sup>\n                    , orthologous mouse models of ADPKD. Nintedanib significantly inhibited cell proliferation and in vitro cyst growth of human ADPKD renal cyst epithelial cells, and cell viability and migration of human ADPKD renal myofibroblasts. Consistently, nintedanib treatment significantly reduced kidney-to-body-weight ratio, renal cystic index, cystic epithelial cell proliferation, and blood-urea nitrogen levels in both the\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>f\/f<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Cre<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>RC\/RC<\/jats:italic>\n                    <\/jats:sup>\n                    mice. There was a corresponding reduction in ERK, AKT, STAT3, and mTOR activity and expression of proproliferative factors, including Yes-associated protein (YAP), c-Myc, and Cyclin D1. Nintedanib treatment significantly reduced fibrosis in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>RC\/RC<\/jats:italic>\n                    <\/jats:sup>\n                    mice, but did not affect renal fibrosis in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>f\/f<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Cre<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Overall, these results suggest that nintedanib may be repurposed to effectively slow cyst growth in ADPKD.\n                  <\/jats:p>","DOI":"10.1038\/s41419-021-04248-9","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T12:21:22Z","timestamp":1634214082000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["The tyrosine-kinase inhibitor Nintedanib ameliorates autosomal-dominant polycystic kidney disease"],"prefix":"10.1038","volume":"12","author":[{"given":"Abeda","family":"Jamadar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreenath M.","family":"Suma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijo","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Fields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5928-9820","authenticated-orcid":false,"given":"James P.","family":"Calvet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0739-9344","authenticated-orcid":false,"given":"Reena","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"4248_CR1","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/nrneph.2011.109","volume":"7","author":"JJ Grantham","year":"2011","unstructured":"Grantham JJ, Mulamalla S, Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2011;7:556\u201366.","journal-title":"Nat Rev Nephrol"},{"key":"4248_CR2","doi-asserted-by":"publisher","first-page":"8936.","DOI":"10.3390\/ijms21238936","volume":"21","author":"M Fragiadaki","year":"2020","unstructured":"Fragiadaki M, Macleod FM, Ong ACM. The controversial role of fibrosis in autosomal dominant polycystic kidney disease. Int J Mol Sci. 2020;21:8936.","journal-title":"Int J Mol Sci"},{"key":"4248_CR3","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.bbadis.2011.06.012","volume":"1812","author":"J Norman","year":"2011","unstructured":"Norman J. Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD). Biochim Biophys Acta. 2011;1812:1327\u201336.","journal-title":"Biochim Biophys Acta"},{"key":"4248_CR4","doi-asserted-by":"publisher","first-page":"3491.","DOI":"10.3390\/ijms19113491","volume":"19","author":"T Yamaoka","year":"2018","unstructured":"Yamaoka T, Kusumoto S, Ando K, Ohba M, Ohmori T. Receptor tyrosine kinase-targeted cancer therapy. Int J Mol Sci. 2018;19:3491.","journal-title":"Int J Mol Sci"},{"key":"4248_CR5","doi-asserted-by":"publisher","first-page":"175346661880061","DOI":"10.1177\/1753466618800618","volume":"12","author":"P Rivera-Ortega","year":"2018","unstructured":"Rivera-Ortega P, Hayton C, Blaikley J, Leonard C, Chaudhuri N. Nintedanib in the management of idiopathic pulmonary fibrosis: clinical trial evidence and real-world experience. Ther Adv Respir Dis. 2018;12:1753466618800618.","journal-title":"Ther Adv Respir Dis"},{"key":"4248_CR6","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.2174\/1389450116666151001104133","volume":"17","author":"M Shabani","year":"2016","unstructured":"Shabani M, Hojjat-Farsangi M. Targeting receptor tyrosine kinases using monoclonal antibodies: the most specific tools for targeted-based cancer therapy. Curr Drug Targets. 2016;17:1687\u2013703.","journal-title":"Curr Drug Targets"},{"key":"4248_CR7","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s004670000495","volume":"16","author":"K Nakanishi","year":"2001","unstructured":"Nakanishi K, Gattone VH 2nd, Sweeney WE, Avner ED. Renal dysfunction but not cystic change is ameliorated by neonatal epidermal growth factor in bpk mice. Pediatr Nephrol. 2001;16:45\u201350.","journal-title":"Pediatr Nephrol"},{"key":"4248_CR8","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1053\/j.gastro.2009.09.005","volume":"138","author":"C Spirli","year":"2010","unstructured":"Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, et al. ERK1\/2-dependent vascular endothelial growth factor signaling sustains cyst growth in polycystin-2 defective mice. Gastroenterology. 2010;138:360\u201371. e367","journal-title":"Gastroenterology"},{"key":"4248_CR9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1046\/j.1523-1755.2000.00829.x","volume":"57","author":"WE Sweeney","year":"2000","unstructured":"Sweeney WE, Chen Y, Nakanishi K, Frost P, Avner ED. Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor. Kidney Int. 2000;57:33\u201340.","journal-title":"Kidney Int"},{"key":"4248_CR10","doi-asserted-by":"publisher","first-page":"188","DOI":"10.5527\/wjn.v6.i4.188","volume":"6","author":"WE Sweeney","year":"2017","unstructured":"Sweeney WE, Frost P, Avner ED. Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease. World J Nephrol. 2017;6:188\u2013200.","journal-title":"World J Nephrol"},{"key":"4248_CR11","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1681\/ASN.2007060665","volume":"19","author":"WE Sweeney Jr.","year":"2008","unstructured":"Sweeney WE Jr., von Vigier RO, Frost P, Avner ED. Src inhibition ameliorates polycystic kidney disease. J Am Soc Nephrology: JASN. 2008;19:1331\u201341.","journal-title":"J Am Soc Nephrology: JASN"},{"key":"4248_CR12","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1038\/sj.ki.5002550","volume":"72","author":"Y Tao","year":"2007","unstructured":"Tao Y, Kim J, Yin Y, Zafar I, Falk S, He Z, et al. VEGF receptor inhibition slows the progression of polycystic kidney disease. Kidney Int. 2007;72:1358\u201366.","journal-title":"Kidney Int"},{"key":"4248_CR13","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1046\/j.1523-1755.2003.00256.x","volume":"64","author":"VE Torres","year":"2003","unstructured":"Torres VE, Sweeney WE Jr., Wang X, Qian Q, Harris PC, Frost P, et al. EGF receptor tyrosine kinase inhibition attenuates the development of PKD in Han:SPRD rats. Kidney Int. 2003;64:1573\u20139.","journal-title":"Kidney Int"},{"key":"4248_CR14","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1021\/jm501562a","volume":"58","author":"GJ Roth","year":"2015","unstructured":"Roth GJ, Binder R, Colbatzky F, Dallinger C, Schlenker-Herceg R, Hilberg F, et al. Nintedanib: from discovery to the clinic. J medicinal Chem. 2015;58:1053\u201363.","journal-title":"J medicinal Chem"},{"key":"4248_CR15","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.4187\/respcare.03023","volume":"59","author":"IA Dimitroulis","year":"2014","unstructured":"Dimitroulis IA. Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis. Respir Care. 2014;59:1450\u20135.","journal-title":"Respir Care"},{"key":"4248_CR16","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1056\/NEJMoa1103690","volume":"365","author":"L Richeldi","year":"2011","unstructured":"Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N. Engl J Med. 2011;365:1079\u201387.","journal-title":"N. Engl J Med"},{"key":"4248_CR17","doi-asserted-by":"publisher","first-page":"4856","DOI":"10.1158\/1078-0432.CCR-14-3036","volume":"21","author":"R Bill","year":"2015","unstructured":"Bill R, Fagiani E, Zumsteg A, Antoniadis H, Johansson D, Haefliger S, et al. Nintedanib is a highly effective therapeutic for neuroendocrine carcinoma of the pancreas (PNET) in the Rip1Tag2 transgenic mouse model. Clin Cancer Res. 2015;21:4856\u201367.","journal-title":"Clin Cancer Res"},{"key":"4248_CR18","doi-asserted-by":"publisher","first-page":"972.","DOI":"10.3390\/ijms17060972","volume":"17","author":"F Liu","year":"2016","unstructured":"Liu F, Zhuang S. Role of receptor tyrosine kinase signaling in renal fibrosis. Int J Mol Sci. 2016;17:972.","journal-title":"Int J Mol Sci"},{"key":"4248_CR19","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/s41416-020-01201-z","volume":"124","author":"R Kato","year":"2021","unstructured":"Kato R, Haratani K, Hayashi H, Sakai K, Sakai H, Kawakami H, et al. Nintedanib promotes antitumour immunity and shows antitumour activity in combination with PD-1 blockade in mice: potential role of cancer-associated fibroblasts. Br J cancer. 2021;124:914\u201324.","journal-title":"Br J cancer"},{"key":"4248_CR20","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.3389\/fphar.2020.01117","volume":"11","author":"F Ruscitti","year":"2020","unstructured":"Ruscitti F, Ravanetti F, Bertani V, Ragionieri L, Mecozzi L, Sverzellati N, et al. Quantification of lung fibrosis in ipf-like mouse model and pharmacological response to treatment by micro-computed tomography. Front Pharmacol. 2020;11:1117.","journal-title":"Front Pharmacol"},{"key":"4248_CR21","doi-asserted-by":"publisher","first-page":"3867198","DOI":"10.1155\/2020\/3867198","volume":"2020","author":"L Wollin","year":"2020","unstructured":"Wollin L, Togbe D, Ryffel B. Effects of nintedanib in an animal model of liver fibrosis. Biomed Res Int. 2020;2020:3867198.","journal-title":"Biomed Res Int"},{"key":"4248_CR22","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1042\/CS20170134","volume":"131","author":"F Liu","year":"2017","unstructured":"Liu F, Wang L, Qi H, Wang J, Wang Y, Jiang W, et al. Nintedanib, a triple tyrosine kinase inhibitor, attenuates renal fibrosis in chronic kidney disease. Clin Sci. 2017;131:2125\u201343.","journal-title":"Clin Sci"},{"key":"4248_CR23","doi-asserted-by":"publisher","first-page":"F721","DOI":"10.1152\/ajprenal.00141.2017","volume":"313","author":"J Wang","year":"2017","unstructured":"Wang J, Zhuang S. Src family kinases in chronic kidney disease. Am J Physiol Ren Physiol. 2017;313:F721\u2013F728.","journal-title":"Am J Physiol Ren Physiol"},{"key":"4248_CR24","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/s41388-019-0988-y","volume":"39","author":"T Azad","year":"2020","unstructured":"Azad T, Nouri K, Janse van Rensburg HJ, Maritan SM, Wu L, Hao Y, et al. A gain-of-functional screen identifies the Hippo pathway as a central mediator of receptor tyrosine kinases during tumorigenesis. Oncogene. 2020;39:334\u201355.","journal-title":"Oncogene"},{"key":"4248_CR25","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1101\/gad.315127.118","volume":"32","author":"J Cai","year":"2018","unstructured":"Cai J, Song X, Wang W, Watnick T, Pei Y, Qian F, et al. A RhoA-YAP-c-Myc signaling axis promotes the development of polycystic kidney disease. Genes Dev. 2018;32:781\u201393.","journal-title":"Genes Dev"},{"key":"4248_CR26","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1681\/ASN.2020020190","volume":"31","author":"N Dwivedi","year":"2020","unstructured":"Dwivedi N, Tao S, Jamadar A, Sinha S, Howard C, Wallace DP, et al. Epithelial vasopressin type-2 receptors regulate myofibroblasts by a YAP-CCN2-dependent mechanism in polycystic kidney disease. J Am Soc Nephrology. 2020;31:1697\u2013710.","journal-title":"J Am Soc Nephrology"},{"key":"4248_CR27","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1038\/ki.2014.427","volume":"87","author":"S Tao","year":"2015","unstructured":"Tao S, Kakade VR, Woodgett JR, Pandey P, Suderman ED, Rajagopal M, et al. Glycogen synthase kinase-3beta promotes cyst expansion in polycystic kidney disease. Kidney Int. 2015;87:1164\u201375.","journal-title":"Kidney Int"},{"key":"4248_CR28","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1158\/1535-7163.MCT-15-0735","volume":"15","author":"X Sun","year":"2016","unstructured":"Sun X, Song Q, He L, Yan L, Liu J, Zhang Q, et al. Receptor tyrosine kinase phosphorylation pattern-based multidrug combination is an effective approach for personalized cancer treatment. Mol Cancer Ther. 2016;15:2508\u201320.","journal-title":"Mol Cancer Ther"},{"key":"4248_CR29","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1046\/j.1523-1755.2001.00768.x","volume":"60","author":"E Bello-Reuss","year":"2001","unstructured":"Bello-Reuss E, Holubec K, Rajaraman S. Angiogenesis in autosomal-dominant polycystic kidney disease. Kidney Int. 2001;60:37\u201345.","journal-title":"Kidney Int"},{"key":"4248_CR30","first-page":"164","volume":"6","author":"S Pandita","year":"2017","unstructured":"Pandita S, Maurya D, Ramachandran V, Verma J, Kohli S, Saxena R, et al. Vascular endothelial growth factor (VEGF) gene promoter polymorphisms and disease progression in north indian cohort with autosomal dominant polycystic kidney disease. Int J Mol Cell Med. 2017;6:164\u201373.","journal-title":"Int J Mol Cell Med"},{"key":"4248_CR31","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1159\/000180269","volume":"31","author":"J Reiterova","year":"2008","unstructured":"Reiterova J, Obeidova H, Lenicek M, Stekrova J, Merta M, Maixnerova D, et al. Influence of VEGF polymorphism on progression of autosomal dominant polycystic kidney disease. Kidney blood Press Res. 2008;31:398\u2013403.","journal-title":"Kidney blood Press Res"},{"key":"4248_CR32","doi-asserted-by":"publisher","first-page":"F773","DOI":"10.1152\/ajprenal.00058.2011","volume":"301","author":"S Raina","year":"2011","unstructured":"Raina S, Honer M, Kramer SD, Liu Y, Wang X, Segerer S, et al. Anti-VEGF antibody treatment accelerates polycystic kidney disease. Am J Physiol Ren Physiol. 2011;301:F773\u2013783.","journal-title":"Am J Physiol Ren Physiol"},{"key":"4248_CR33","doi-asserted-by":"publisher","first-page":"791","DOI":"10.4111\/kju.2015.56.12.791","volume":"56","author":"T Grenader","year":"2015","unstructured":"Grenader T, Shavit L. Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy. Korean J Urol. 2015;56:791\u20135.","journal-title":"Korean J Urol"},{"key":"4248_CR34","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/ki.1991.239","volume":"40","author":"GA Herrera","year":"1991","unstructured":"Herrera GA. C-erb B-2 amplification in cystic renal disease. Kidney Int. 1991;40:509\u201313.","journal-title":"Kidney Int"},{"key":"4248_CR35","first-page":"131","volume":"61","author":"PD Wilson","year":"1993","unstructured":"Wilson PD, Du J, Norman JT. Autocrine, endocrine and paracrine regulation of growth abnormalities in autosomal dominant polycystic kidney disease. Eur J Cell Biol. 1993;61:131\u20138.","journal-title":"Eur J Cell Biol"},{"key":"4248_CR36","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1006\/bmme.1997.2583","volume":"61","author":"NT Kuo","year":"1997","unstructured":"Kuo NT, Norman JT, Wilson PD. Acidic FGF regulation of hyperproliferation of fibroblasts in human autosomal dominant polycystic kidney disease. Biochem Mol Med. 1997;61:178\u201391.","journal-title":"Biochem Mol Med"},{"key":"4248_CR37","doi-asserted-by":"publisher","first-page":"12451","DOI":"10.1002\/jcp.28094","volume":"234","author":"T Malekshahabi","year":"2019","unstructured":"Malekshahabi T, Khoshdel Rad N, Serra AL, Moghadasali R. Autosomal dominant polycystic kidney disease: disrupted pathways and potential therapeutic interventions. J Cell Physiol. 2019;234:12451\u201370.","journal-title":"J Cell Physiol"},{"key":"4248_CR38","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1093\/jmcb\/mjw022","volume":"8","author":"VR Kakade","year":"2016","unstructured":"Kakade VR, Tao S, Rajagopal M, Zhou X, Li X, Yu AS, et al. A cAMP and CREB-mediated feed-forward mechanism regulates GSK3beta in polycystic kidney disease. J Mol cell Biol. 2016;8:464\u201376.","journal-title":"J Mol cell Biol"},{"key":"4248_CR39","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1056\/NEJMcp0804458","volume":"359","author":"JJ Grantham","year":"2008","unstructured":"Grantham JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N. Engl J Med. 2008;359:1477\u201385.","journal-title":"N. Engl J Med"},{"key":"4248_CR40","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1100\/tsw.2007.274","volume":"7","author":"S Ibrahim","year":"2007","unstructured":"Ibrahim S. Increased apoptosis and proliferative capacity are early events in cyst formation in autosomal-dominant, polycystic kidney disease. ScientificWorldJournal. 2007;7:1757\u201367.","journal-title":"ScientificWorldJournal"},{"key":"4248_CR41","doi-asserted-by":"publisher","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. Inflammation and fibrosis in polycystic kidney disease. Results Probl Cell Differ. 2017;60:323\u201344.","journal-title":"Results Probl Cell Differ"},{"key":"4248_CR42","doi-asserted-by":"publisher","first-page":"F1423","DOI":"10.1152\/ajprenal.00275.2007","volume":"293","author":"T Weimbs","year":"2007","unstructured":"Weimbs T. Polycystic kidney disease and renal injury repair: common pathways, fluid flow, and the function of polycystin-1. Am J Physiol Ren Physiol. 2007;293:F1423\u20131432.","journal-title":"Am J Physiol Ren Physiol"},{"key":"4248_CR43","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1124\/jpet.113.208223","volume":"349","author":"L Wollin","year":"2014","unstructured":"Wollin L, Maillet I, Quesniaux V, Holweg A, Ryffel B. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp therapeutics. 2014;349:209\u201320.","journal-title":"J Pharmacol Exp therapeutics"},{"key":"4248_CR44","doi-asserted-by":"publisher","first-page":"4257","DOI":"10.1172\/JCI64313","volume":"122","author":"K Hopp","year":"2012","unstructured":"Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, et al. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Investig. 2012;122:4257\u201373.","journal-title":"J Clin Investig"},{"key":"4248_CR45","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.kint.2018.06.025","volume":"94","author":"EK Kleczko","year":"2018","unstructured":"Kleczko EK, Marsh KH, Tyler LC, Furgeson SB, Bullock BL, Altmann CJ, et al. CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression. Kidney Int. 2018;94:1127\u201340.","journal-title":"Kidney Int"},{"key":"4248_CR46","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1681\/ASN.2011010084","volume":"22","author":"A Karihaloo","year":"2011","unstructured":"Karihaloo A, Koraishy F, Huen SC, Lee Y, Merrick D, Caplan MJ, et al. Macrophages promote cyst growth in polycystic kidney disease. J Am Soc Nephrology: JASN. 2011;22:1809\u201314.","journal-title":"J Am Soc Nephrology: JASN"},{"key":"4248_CR47","doi-asserted-by":"publisher","first-page":"F650","DOI":"10.1152\/ajprenal.00516.2014","volume":"308","author":"R Norregaard","year":"2015","unstructured":"Norregaard R, Tao S, Nilsson L, Woodgett JR, Kakade V, Yu AS, et al. Glycogen synthase kinase 3alpha regulates urine concentrating mechanism in mice. Am J Physiol Ren Physiol. 2015;308:F650\u2013660.","journal-title":"Am J Physiol Ren Physiol"},{"key":"4248_CR48","first-page":"931","volume":"8","author":"SP Singh","year":"2015","unstructured":"Singh SP, Tao S, Fields TA, Webb S, Harris RC, Rao R. Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice. Dis Model Mech. 2015;8:931\u201340.","journal-title":"Dis Model Mech"},{"key":"4248_CR49","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-1-59745-352-3_3","volume":"466","author":"L Grimwood","year":"2009","unstructured":"Grimwood L, Masterson R. Propagation and culture of renal fibroblasts. Methods Mol Biol. 2009;466:25\u201337.","journal-title":"Methods Mol Biol"},{"key":"4248_CR50","doi-asserted-by":"publisher","first-page":"13597","DOI":"10.1096\/fj.202000526RR","volume":"34","author":"S Sinha","year":"2020","unstructured":"Sinha S, Dwivedi N, Woodgett J, Tao S, Howard C, Fields TA, et al. Glycogen synthase kinase-3beta inhibits tubular regeneration in acute kidney injury by a FoxM1-dependent mechanism. FASEB J. 2020;34:13597\u2013608.","journal-title":"FASEB J"},{"key":"4248_CR51","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1038\/s41388-019-1059-0","volume":"39","author":"S Sinha","year":"2020","unstructured":"Sinha S, Dwivedi N, Tao S, Jamadar A, Kakade VR, Neil MO, et al. Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy. Oncogene. 2020;39:1231\u201345.","journal-title":"Oncogene"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-04248-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-04248-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-04248-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T04:16:37Z","timestamp":1669954597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-04248-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["4248"],"URL":"https:\/\/doi.org\/10.1038\/s41419-021-04248-9","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]},"assertion":[{"value":"17 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal study protocols were approved by the KUMC Institutional Animal Care and Use Committee.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"947"}}