{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:02:40Z","timestamp":1792800160079,"version":"4.5.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Directorate General of Higher Education, Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia"},{"name":"The NWO\u2013FAPESP joint grant on healthy aging, executed by the Dutch Research Council","award":["ZonMw, grant no. 457002002"],"award-info":[{"award-number":["ZonMw, grant no. 457002002"]}],"id":[{"id":"https:\/\/ror.org\/04jsz6e67","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001826","name":"The Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["ZonMw, grant no. 40-00703-97-12480"],"award-info":[{"award-number":["ZonMw, grant no. 40-00703-97-12480"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Management of chronic kidney disease (CKD) remains a major challenge due limited therapeutic options to reverse fibrosis, which is a critical feature in CKD. Partial epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs) is a key driver of fibrosis, and has become an important focus for kidney protection strategies. Blood platelets, a major source of circulating transforming growth factor beta (TGF-\u03b2), are implicated in pathogenesis of CKD, but their involvement in EMT and kidney fibrosis remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used two mouse models of renal fibrosis\u2014diabetic kidney disease (DKD) and unilateral ureter obstruction (UUO)\u2014to examine the connection between platelets, partial EMT, and fibrosis. Platelet inhibition or depletion was performed to assess EMT, cell cycle arrest, and fibrosis. In vitro, platelets were applied to TECs and kidney organoids. To determine the role of TGF-\u03b2 signaling, we used TGF-\u03b2RI inhibitor. Expression of EMT, and fibrosis markers, as well as TGF-\u03b21 signaling, were analyzed using western blot, reverse transcription quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunostaining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In both animal models, platelet inhibition or depletion resulted in reduced expression of cell cycle arrest marker p21, partial EMT and fibrosis. In vitro, activated platelets stimulated cell cycle arrest, EMT, and fibrosis in TECs and kidney organoids. Chronically injured TECs experience cell-cycle arrest which promote a paracrine EMT program in TECs, jointly leading to fibrosis. This platelet-mediated effect on cell cycle arrest and EMT was driven by TGF-\u03b21 signaling, as selective inhibition of the TGF-\u03b2 receptor rescued these dysfunctional phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study demonstrates that platelets activate the TGF-\u03b21 pathway, leading to cell cycle arrest, EMT and renal fibrosis. These findings suggest that antiplatelet therapies may have potential renoprotective effects by protecting tubular homeostasis, attenuating partial EMT and fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-025-01355-7","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T11:51:19Z","timestamp":1761738679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Platelets induce epithelial to mesenchymal transition in renal proximal tubular epithelial cells through TGF-\u03b2 signaling pathway"],"prefix":"10.1186","volume":"31","author":[{"given":"Ukhti Jamil","family":"Rustiasari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Uil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nike","family":"Claessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loes","family":"Butter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Florquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Tammaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris J.T.H.","family":"Roelofs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"issue":"Suppl 2","key":"1355_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1093\/ckj\/sfae296","volume":"17","author":"D Abasheva","year":"2024","unstructured":"Abasheva D, Ortiz A, Fernandez-Fernandez B. GLP-1 receptor agonists in patients with chronic kidney disease and either overweight or obesity. Clin Kidney J. 2024;17(Suppl 2):19\u201335. https:\/\/doi.org\/10.1093\/ckj\/sfae296. Published 2024 Nov 22.","journal-title":"Clin Kidney J"},{"issue":"2","key":"1355_CR2","doi-asserted-by":"publisher","first-page":"100943","DOI":"10.1016\/j.xkme.2024.100943","volume":"7","author":"P Amornritvanich","year":"2024","unstructured":"Amornritvanich P, Anothaisintawee T, Attia J, McKay GJ, Thakkinstian A. Efficacy of mineralocorticoid receptor antagonists on kidney and cardiovascular outcomes in patients with chronic kidney disease: an umbrella review. Kidney Med. 2024;7(2):100943. https:\/\/doi.org\/10.1016\/j.xkme.2024.100943. Published 2024 Dec 13.","journal-title":"Kidney Med"},{"issue":"1","key":"1355_CR3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.2215\/CJN.04100321","volume":"17","author":"CCFMJ Baaten","year":"2022","unstructured":"Baaten CCFMJ, Schr\u00f6er JR, Floege J, et al. Platelet abnormalities in CKD and their implications for antiplatelet therapy. Clin J Am Soc Nephrol. 2022;17(1):155\u201370. https:\/\/doi.org\/10.2215\/CJN.04100321.","journal-title":"Clin J Am Soc Nephrol"},{"issue":"1","key":"1355_CR4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S2213-8587(24)00271-7","volume":"13","author":"SV Badve","year":"2025","unstructured":"Badve SV, Bilal A, Lee MMY, et al. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2025;13(1):15\u201328. https:\/\/doi.org\/10.1016\/S2213-8587(24)00271-7.","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"4","key":"1355_CR5","doi-asserted-by":"publisher","first-page":"e158","DOI":"10.1159\/000094967","volume":"104","author":"A Benigni","year":"2006","unstructured":"Benigni A, Zoja C, Campana M, Corna D, Sangalli F, Rottoli D, et al. Beneficial effect of TGF\u03b2 antagonism in treating diabetic nephropathy depends on when treatment is started. Nephron Experimental Nephrol. 2006;104(4):e158\u201368.","journal-title":"Nephron Experimental Nephrol"},{"key":"1355_CR6","doi-asserted-by":"publisher","unstructured":"Cao H, Li R, Ling L, Ni G. PF4 Silencing Promotes Trophoblast Cell Proliferation, Migration, Invasion and EMT by Regulating SOCS3\/STAT3 Signaling Pathway. Endocr Metab Immune Disord Drug Targets Published online Dec. 2024;17. https:\/\/doi.org\/10.2174\/0118715303299470240723060939. Published 2024 Dec 17.","DOI":"10.2174\/0118715303299470240723060939"},{"issue":"12","key":"1355_CR7","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1111\/jcmm.12919","volume":"20","author":"SY Choi","year":"2016","unstructured":"Choi SY, Kee HJ, Kurz T, et al. Class I HDACs specifically regulate E-cadherin expression in human renal epithelial cells. J Cell Mol Med. 2016;20(12):2289\u201398. https:\/\/doi.org\/10.1111\/jcmm.12919.","journal-title":"J Cell Mol Med"},{"issue":"1","key":"1355_CR8","first-page":"1","volume":"9","author":"Z Deng","year":"2024","unstructured":"Deng Z, Fan T, Xiao C, Tian H, Zheng Y, Li C, et al. TGF-\u03b2 signaling in health, disease, and therapeutics. Signal Transduct Target Ther. 2024;9(1):1\u201340.","journal-title":"Signal Transduct Target Ther"},{"key":"1355_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.607483","author":"J Di Gregorio","year":"2020","unstructured":"Di Gregorio J, Robuffo I, Spalletta S, Giambuzzi G, De Iuliis V, Toniato E, et al. The epithelial-to-mesenchymal transition as a possible therapeutic target in fibrotic disorders. Front Cell Dev Biol. 2020. https:\/\/doi.org\/10.3389\/fcell.2020.607483.","journal-title":"Front Cell Dev Biol"},{"issue":"6","key":"1355_CR10","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1172\/JCI72267","volume":"124","author":"JS Duffield","year":"2014","unstructured":"Duffield JS. Cellular and molecular mechanisms in kidney fibrosis. J Clin Invest. 2014;124(6):2299\u2013306. https:\/\/doi.org\/10.1172\/JCI72267.","journal-title":"J Clin Invest"},{"key":"1355_CR11","unstructured":"Francis A, Harhay MN, Ong ACM, Tummalapalli SL, Ortiz A, Fogo AB et al. Chronic kidney disease and the global public health agenda: an international consensus. Nature Reviews Nephrology. 2024;20(20):1\u201313. Available from: https:\/\/www.nature.com\/articles\/s41581-024-00820-6"},{"issue":"4","key":"1355_CR12","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1159\/000525090","volume":"8","author":"S Gong","year":"2022","unstructured":"Gong S, Wang C, Xiong J, Zhao J, Yang K. Activated platelets, the booster of chronic kidney disease and cardiovascular complications. Kidney Dis. 2022;8(4):297\u2013307.","journal-title":"Kidney Dis"},{"key":"1355_CR13","doi-asserted-by":"publisher","unstructured":"Grande MT, S\u00e1nchez-Laorden B, L\u00f3pez-Blau C et al. Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease [published correction appears in Nat Med. 2016;22(2):217. https:\/\/doi.org\/10.1038\/nm0216-217d. Nat Med. 2015;21(9):989\u2013997. doi:10.1038\/nm.3901.","DOI":"10.1038\/nm0216-217d"},{"issue":"3","key":"1355_CR14","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.ygyno.2019.02.026","volume":"153","author":"Y Guo","year":"2019","unstructured":"Guo Y, Cui W, Pei Y, Xu D. Platelets promote invasion and induce epithelial to mesenchymal transition in ovarian cancer cells by TGF-\u03b2 signaling pathway. Gynecol Oncol. 2019;153(3):639\u201350.","journal-title":"Gynecol Oncol"},{"issue":"2","key":"1355_CR15","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.kint.2016.08.006","volume":"91","author":"MPB Jansen","year":"2017","unstructured":"Jansen MPB, Emal D, Teske GJD, Dessing MC, Florquin S, Roelofs JJTH. Release of extracellular DNA influences renal ischemia reperfusion injury by platelet activation and formation of neutrophil extracellular traps. Kidney Int. 2017;91(2):352\u201364.","journal-title":"Kidney Int"},{"key":"1355_CR16","doi-asserted-by":"crossref","unstructured":"Jansen J, van den Berge BT, van den Broek M, Maas RJ, Daviran D, Willemsen B et al. Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling. Development. 2022;149(9). Available from: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9148570\/","DOI":"10.1242\/dev.200198"},{"issue":"6","key":"1355_CR17","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1172\/JCI39104","volume":"119","author":"R Kalluri","year":"2009","unstructured":"Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420\u20138.","journal-title":"J Clin Invest"},{"key":"1355_CR18","doi-asserted-by":"crossref","unstructured":"Karolczak K, Cezary Wata\u0142a. Blood Platelets as an Important but Underrated Circulating Source of TGF\u03b2. International Journal of Molecular Sciences. 2021;22(9):4492\u20132. Available from: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8123509\/","DOI":"10.3390\/ijms22094492"},{"issue":"8","key":"1355_CR19","doi-asserted-by":"publisher","first-page":"e43584","DOI":"10.1371\/journal.pone.0043584","volume":"7","author":"C Keller","year":"2012","unstructured":"Keller C, Kroening S, Zuehlke J, Kunath F, Krueger B, Goppelt-Struebe M. Distinct mesenchymal alterations in N-cadherin and E-cadherin positive primary renal epithelial cells. PLoS One. 2012;7(8):e43584. https:\/\/doi.org\/10.1371\/journal.pone.0043584.","journal-title":"PLoS One"},{"key":"1355_CR20","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0199","author":"AO Khan","year":"2023","unstructured":"Khan AO, Rodriguez-Romera A, Reyat JS, Olijnik AA, Colombo M, Wang G, et al. Human bone marrow organoids for disease modeling, discovery, and validation of therapeutic targets in hematologic malignancies. Cancer Discov. 2023. https:\/\/doi.org\/10.1158\/2159-8290.CD-22-0199.","journal-title":"Cancer Discov"},{"issue":"3","key":"1355_CR21","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/path.4253","volume":"231","author":"R Kramann","year":"2013","unstructured":"Kramann R, DiRocco DP, Humphreys BD. Understanding the origin, activation and regulation of matrix-producing myofibroblasts for treatment of fibrotic disease. J Pathol. 2013;231(3):273\u201389. https:\/\/doi.org\/10.1002\/path.4253.","journal-title":"J Pathol"},{"issue":"8","key":"1355_CR22","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/nm.3218","volume":"19","author":"VS LeBleu","year":"2013","unstructured":"LeBleu VS, Taduri G, O\u2019Connell J, et al. Origin and function of myofibroblasts in kidney fibrosis. Nat Med. 2013;19(8):1047\u201353. https:\/\/doi.org\/10.1038\/nm.3218.","journal-title":"Nat Med"},{"key":"1355_CR23","doi-asserted-by":"crossref","unstructured":"Lev PR, Salim JP, Marta RF, Osorio MJM, Goette NP, Molinas FC. Platelets possess functional TGF-beta receptors and Smad2 protein. Platelets. 2007;18(1):35\u201342. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/17365852\/","DOI":"10.1080\/09537100600800743"},{"issue":"4","key":"1355_CR24","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3390\/cells4040631","volume":"4","author":"I Loeffler","year":"2015","unstructured":"Loeffler I, Wolf G. Epithelial-to-mesenchymal transition in diabetic nephropathy: fact or fiction?? Cells. 2015;4(4):631\u201352. https:\/\/doi.org\/10.3390\/cells4040631.","journal-title":"Cells"},{"issue":"10","key":"1355_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101118","volume":"8","author":"CY Loh","year":"2019","unstructured":"Loh CY, Chai JY, Tang TF, et al. The E-cadherin and N-cadherin switch in epithelial-to-mesenchymal transition: signaling, therapeutic implications, and challenges. Cells. 2019;8(10): 1118. https:\/\/doi.org\/10.3390\/cells8101118.","journal-title":"Cells"},{"issue":"9","key":"1355_CR26","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1038\/nm.3902","volume":"21","author":"S Lovisa","year":"2015","unstructured":"Lovisa S, LeBleu VS, Tampe B, Sugimoto H, Vadnagara K, Carstens JL, et al. Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat Med. 2015;21(9):998\u20131009.","journal-title":"Nat Med"},{"issue":"10","key":"1355_CR27","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.tem.2016.06.004","volume":"27","author":"S Lovisa","year":"2016","unstructured":"Lovisa S, Zeisberg M, Kalluri R. Partial epithelial-to-mesenchymal transition and other new mechanisms of kidney fibrosis. Trends Endocrinol Metab. 2016;27(10):681\u201395.","journal-title":"Trends Endocrinol Metab"},{"issue":"7","key":"1355_CR28","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1038\/sj.ki.5001775","volume":"70","author":"JA Moon","year":"2006","unstructured":"Moon JA, Kim HT, Cho IS, Sheen YY, Kim DK. IN-1130, a novel transforming growth factor-\u03b2 type I receptor kinase (ALK5) inhibitor, suppresses renal fibrosis in obstructive nephropathy. Kidney Int. 2006;70(7):1234\u201343.","journal-title":"Kidney Int"},{"key":"1355_CR29","doi-asserted-by":"crossref","unstructured":"Nieto M, Angela, Huang RJ, Jackson Rebecca A, Thiery J.EMT:2016. Cell. 2016;166(1):21\u201345. Available from: https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(16)30796-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867416307966%3Fshowall%3Dtrue","DOI":"10.1016\/j.cell.2016.06.028"},{"issue":"12","key":"1355_CR30","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.3390\/ph15121485","volume":"15","author":"CH Park","year":"2022","unstructured":"Park CH, Yoo TH. TGF-\u03b2 inhibitors for therapeutic management of kidney fibrosis. Pharmaceuticals. 2022;15(12):1485.","journal-title":"Pharmaceuticals"},{"issue":"23","key":"1355_CR31","doi-asserted-by":"publisher","first-page":"21113","DOI":"10.1074\/jbc.M211304200","volume":"278","author":"H Peinado","year":"2003","unstructured":"Peinado H, Quintanilla M, Cano A. Transforming growth factor \u03b2-1 induces snail transcription factor in epithelial cell lines. J Biol Chem. 2003;278(23):21113\u201323.","journal-title":"J Biol Chem"},{"key":"1355_CR32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1472-6793-4-10","volume":"4","author":"WC Prozialeck","year":"2004","unstructured":"Prozialeck WC, Lamar PC, Appelt DM. Differential expression of E-cadherin, N-cadherin and beta-catenin in proximal and distal segments of the rat nephron. BMC Physiol. 2004;4:10. https:\/\/doi.org\/10.1186\/1472-6793-4-10. Published 2004 May 17.","journal-title":"BMC Physiol"},{"key":"1355_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03322-y","author":"R Qi","year":"2021","unstructured":"Qi R, Wang J, Jiang Y, Qiu Y, Xu M, Rong R, et al. Snai1-induced partial epithelial\u2013mesenchymal transition orchestrates p53\u2013p21-mediated G2\/M arrest in the progression of renal fibrosis via NF-\u03baB-mediated inflammation. Cell Death Dis. 2021. https:\/\/doi.org\/10.1038\/s41419-020-03322-y.","journal-title":"Cell Death Dis"},{"issue":"15","key":"1355_CR34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158270","volume":"23","author":"UJ Rustiasari","year":"2022","unstructured":"Rustiasari UJ, Roelofs JJ. The role of platelets in diabetic kidney disease. Int J Mol Sci. 2022;23(15): 8270. https:\/\/doi.org\/10.3390\/ijms23158270.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1355_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-016-0502-x","volume":"15","author":"SJ Serrano-Gomez","year":"2016","unstructured":"Serrano-Gomez SJ, Maziveyi M, Alahari SK. Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications. Mol Cancer. 2016;15(1): 18.","journal-title":"Mol Cancer"},{"issue":"3","key":"1355_CR36","doi-asserted-by":"publisher","first-page":"e0120132","DOI":"10.1371\/journal.pone.0120132","volume":"10","author":"A Slusser","year":"2015","unstructured":"Slusser A, Bathula CS, Sens DA, et al. Cadherin expression, vectorial active transport, and metallothionein isoform 3 mediated EMT\/MET responses in cultured primary and immortalized human proximal tubule cells. PLoS One. 2015;10(3):e0120132. https:\/\/doi.org\/10.1371\/journal.pone.0120132. (Published 2015 Mar 24).","journal-title":"PLoS One"},{"issue":"9","key":"1355_CR37","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1038\/nprot.2016.098","volume":"11","author":"M Takasato","year":"2016","unstructured":"Takasato M, Er PX, Chiu HS, Little MH. Generation of kidney organoids from human pluripotent stem cells. Nat Protoc. 2016;11(9):1681\u201392.","journal-title":"Nat Protoc"},{"key":"1355_CR38","doi-asserted-by":"crossref","unstructured":"Takemoto A, Okitaka M, Takagi S, Takami M, Sato S, Nishio M et al. A critical role of platelet TGF-\u03b2 release in podoplanin-mediated tumour invasion and metastasis. Scientific Reports. 2017;7(1). Available from: https:\/\/www.nature.com\/articles\/srep42186\/","DOI":"10.1038\/srep42186"},{"issue":"11","key":"1355_CR39","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1292\/jvms.17-0439","volume":"79","author":"N Terada","year":"2017","unstructured":"Terada N, Karim MR, Izawa T, Kuwamura M, Yamate J. Immunolocalization of \u03b2-catenin, E-cadherin and N-cadherin in neonate and adult rat kidney. J Vet Med Sci. 2017;79(11):1785\u201390. https:\/\/doi.org\/10.1292\/jvms.17-0439.","journal-title":"J Vet Med Sci"},{"issue":"5","key":"1355_CR40","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","volume":"139","author":"JP Thiery","year":"2009","unstructured":"Thiery JP, Acloque H, Huang RYJ, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871\u201390.","journal-title":"Cell"},{"key":"1355_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2022.110161","volume":"194","author":"S Tsukamoto","year":"2022","unstructured":"Tsukamoto S, Morita R, Yamada T, et al. Cardiovascular and kidney outcomes of combination therapy with sodium-glucose cotransporter-2 inhibitors and mineralocorticoid receptor antagonists in patients with type 2 diabetes and chronic kidney disease: a systematic review and network meta-analysis. Diabetes Res Clin Pract. 2022;194: 110161. https:\/\/doi.org\/10.1016\/j.diabres.2022.110161.","journal-title":"Diabetes Res Clin Pract"},{"issue":"10","key":"1355_CR42","doi-asserted-by":"publisher","first-page":"13750","DOI":"10.1096\/fj.202000897R","volume":"34","author":"M Uil","year":"2020","unstructured":"Uil M, Butter LM, Nike Claessen, Larsen PW, Sandrine Florquin. Joris. Platelet Inhibition by Ticagrelor is protective against diabetic nephropathy in mice. FASEB J. 2020;34(10):13750\u201361.","journal-title":"FASEB J"},{"key":"1355_CR43","doi-asserted-by":"crossref","unstructured":"Wen H, Yang D, Xie C, Shi F, Liu Y, Zhang J et al. Comparison of trend in chronic kidney disease burden between china, japan, the united kingdom, and the united States. Front Public Health. 2022;10.","DOI":"10.3389\/fpubh.2022.999848"},{"issue":"6","key":"1355_CR44","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1177\/11297298231192386","volume":"25","author":"Y Xiao","year":"2024","unstructured":"Xiao Y, Martinez L, Zigmond Z, et al. Functions for platelet factor 4 (PF4\/CXCL4) and its receptors in fibroblast-myofibroblast transition and fibrotic failure of arteriovenous fistulas (AVFs). J Vasc Access. 2024;25(6):1911\u201324. https:\/\/doi.org\/10.1177\/11297298231192386.","journal-title":"J Vasc Access"},{"issue":"6","key":"1355_CR45","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.devcel.2008.05.009","volume":"14","author":"J Yang","year":"2008","unstructured":"Yang J, Weinberg RA. Epithelial-Mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6):818\u201329.","journal-title":"Dev Cell"},{"issue":"7","key":"1355_CR46","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1016\/j.ekir.2022.04.094","volume":"7","author":"K Yau","year":"2022","unstructured":"Yau K, Dharia A, Alrowiyti I, Cherney DZI. Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations. Kidney Int Rep. 2022;7(7):1463\u201376. https:\/\/doi.org\/10.1016\/j.ekir.2022.04.094.","journal-title":"Kidney Int Rep"},{"key":"1355_CR47","doi-asserted-by":"crossref","unstructured":"Yousef Yengej FA, Jansen J, Ammerlaan CME, Dilmen E, Pou Casellas C, Masereeuw R et al. Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids. Proceedings of the National Academy of Sciences of the United States of America. 2023;120(6):e2216836120. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/36724260\/","DOI":"10.1073\/pnas.2216836120"},{"key":"1355_CR48","doi-asserted-by":"crossref","unstructured":"Yun SH, Sim EH, Goh RY, Park JI, Han JY. Platelet Activation: The Mechanisms and Potential Biomarkers. BioMed Research International. 2016;2016:1\u20135. Available from: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4925965\/","DOI":"10.1155\/2016\/9060143"},{"issue":"3","key":"1355_CR49","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s00109-003-0517-9","volume":"82","author":"M Zeisberg","year":"2004","unstructured":"Zeisberg M, Kalluri R. The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med. 2004;82(3):175\u201381.","journal-title":"J Mol Med"},{"key":"1355_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01808-7","author":"S Zhang","year":"2021","unstructured":"Zhang S, Fan Y, Qin L, Fang X, Zhang C, Yue J, et al. IL-1\u03b2 augments TGF-\u03b2 inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics. Respir Res. 2021. https:\/\/doi.org\/10.1186\/s12931-021-01808-7.","journal-title":"Respir Res"},{"issue":"22","key":"1355_CR51","doi-asserted-by":"publisher","first-page":"13208","DOI":"10.1111\/jcmm.15933","volume":"24","author":"X Zhao","year":"2020","unstructured":"Zhao X, Yang Y, Yu H, Wu W, Sun Y, Pan Y, et al. Polydatin inhibits ZEB1-invoked epithelial\u2010mesenchymal transition in fructose\u2010induced liver fibrosis. J Cell Mol Med. 2020;24(22):13208\u201322.","journal-title":"J Cell Mol Med"}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-025-01355-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10020-025-01355-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-025-01355-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:28:19Z","timestamp":1781612899000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s10020-025-01355-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1355"],"URL":"https:\/\/doi.org\/10.1186\/s10020-025-01355-7","relation":{},"ISSN":["1528-3658"],"issn-type":[{"value":"1528-3658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"14 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"Animal experiment was granted permission by the Animal Care and use Committee of University of Amsterdam (reference number DKD: DPA109; UUO: DPA4), and all procedures were followed in compliance with Dutch government regulations. All participant signed informed consent, and this study was performed under the approval of the Medical Research Ethics Committees (MREC) of Amsterdam UMC (reference number 2024.0885), in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"No applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"318"}}