{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T21:23:37Z","timestamp":1767734617895,"version":"3.48.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100011103","name":"Rann\u00eds","doi-asserted-by":"publisher","award":["217707-051"],"award-info":[{"award-number":["217707-051"]}],"id":[{"id":"10.13039\/501100011103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004103","name":"Landsp\u00edtali H\u00e1sk\u00f3lasj\u00fakrah\u00fas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004103","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s00109-025-02625-x","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T21:19:33Z","timestamp":1767734373000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["2,8-Dihydroxyadenine disrupts epithelial integrity and alters kidney cell phenotype in vitro"],"prefix":"10.1007","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-9010","authenticated-orcid":false,"given":"Hildur Run","family":"Helgudottir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-1702","authenticated-orcid":false,"given":"Runolfur","family":"Palsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4204-9342","authenticated-orcid":false,"given":"Vidar Orn","family":"Edvardsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9645-9665","authenticated-orcid":false,"given":"Thorarinn","family":"Gudjonsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"issue":"3","key":"2625_CR1","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1053\/j.ajkd.2015.10.023","volume":"67","author":"HL Runolfsdottir","year":"2016","unstructured":"Runolfsdottir HL et al (2016) Kidney disease in adenine phosphoribosyltransferase deficiency. Am J Kidney Dis 67(3):431\u20138","journal-title":"Am J Kidney Dis"},{"issue":"10","key":"2625_CR2","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1007\/s00467-012-2329-z","volume":"28","author":"VO Edvardsson","year":"2013","unstructured":"Edvardsson VO et al (2013) Hereditary causes of kidney stones and chronic kidney disease. Pediatr Nephrol 28(10):1923\u20131942","journal-title":"Pediatr Nephrol"},{"issue":"3","key":"2625_CR3","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1053\/ajkd.2001.26826","volume":"38","author":"V Edvardsson","year":"2001","unstructured":"Edvardsson V et al (2001) Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis 38(3):473\u201380","journal-title":"Am J Kidney Dis"},{"issue":"5","key":"2625_CR4","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/ki.2013.207","volume":"84","author":"F Knauf","year":"2013","unstructured":"Knauf F et al (2013) NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int 84(5):895\u2013901","journal-title":"Kidney Int"},{"issue":"1","key":"2625_CR5","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1172\/JCI63679","volume":"123","author":"SR Mulay","year":"2013","unstructured":"Mulay SR et al (2013) Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1beta secretion. J Clin Invest 123(1):236\u2013246","journal-title":"J Clin Invest"},{"issue":"3","key":"2625_CR6","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.kint.2016.03.035","volume":"90","author":"I Ludwig-Portugall","year":"2016","unstructured":"Ludwig-Portugall I et al (2016) An NLRP3-specific inflammasome inhibitor attenuates crystal-induced kidney fibrosis in mice. Kidney Int 90(3):525\u201339","journal-title":"Kidney Int"},{"issue":"4","key":"2625_CR7","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1681\/ASN.2019080827","volume":"31","author":"BM Klinkhammer","year":"2020","unstructured":"Klinkhammer BM et al (2020) Cellular and molecular mechanisms of kidney injury in 2,8-dihydroxyadenine nephropathy. J Am Soc Nephrol 31(4):799\u2013816","journal-title":"J Am Soc Nephrol"},{"key":"2625_CR8","unstructured":"Shah A, SW Leslie, Ramakrishnan S, Hyperoxaluria, in StatPearls. 2025, StatPearls Publishing"},{"issue":"1","key":"2625_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/labinvest.2010.167","volume":"91","author":"P Peerapen","year":"2011","unstructured":"Peerapen P, Thongboonkerd V (2011) Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells. Lab Invest 91(1):97\u2013105","journal-title":"Lab Invest"},{"issue":"1","key":"2625_CR10","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1080\/0886022X.2017.1305968","volume":"39","author":"L Yu","year":"2017","unstructured":"Yu L et al (2017) Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS\/Akt\/p38 MAPK signaling pathway. Ren Fail 39(1):440\u2013451","journal-title":"Ren Fail"},{"issue":"12","key":"2625_CR11","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1097\/01.ASN.0000099380.18995.F7","volume":"14","author":"M Asselman","year":"2003","unstructured":"Asselman M et al (2003) Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured\/regenerating tubular epithelial cells in rat kidneys. J Am Soc Nephrol 14(12):3155\u201366","journal-title":"J Am Soc Nephrol"},{"issue":"2","key":"2625_CR12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s00240-019-01155-9","volume":"48","author":"B Wang","year":"2020","unstructured":"Wang B et al (2020) MiRNA-34a inhibits cell adhesion by targeting CD44 in human renal epithelial cells: implications for renal stone disease. Urolithiasis 48(2):109\u2013116","journal-title":"Urolithiasis"},{"key":"2625_CR13","doi-asserted-by":"crossref","unstructured":"Koul S et al (2012) Genome-wide analysis of differentially expressed genes in HK-2 cells, a line of human kidney epithelial cells in response to oxalate. PLoS One 7(9):e43886","DOI":"10.1371\/journal.pone.0043886"},{"key":"2625_CR14","doi-asserted-by":"publisher","first-page":"1004610","DOI":"10.3389\/fgene.2022.1004610","volume":"13","author":"L Zhang","year":"2022","unstructured":"Zhang L et al (2022) The expression of apoptosis related genes in HK-2 cells overexpressing PPM1K was determined by RNA-seq analysis. Front Genet 13:1004610","journal-title":"Front Genet"},{"issue":"7","key":"2625_CR15","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/nmeth.4324","volume":"14","author":"H Pimentel","year":"2017","unstructured":"Pimentel H et al (2017) Differential analysis of RNA-seq incorporating quantification uncertainty. Nat Methods 14(7):687\u2013690","journal-title":"Nat Methods"},{"issue":"43","key":"2625_CR16","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102(43):15545\u201315550","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2625_CR17","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon A et al (2015) The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst 1(6):417\u2013425","journal-title":"Cell Syst"},{"issue":"3","key":"2625_CR18","first-page":"243","volume":"61","author":"RL Omeir","year":"2011","unstructured":"Omeir RL et al (2011) Heterogeneity of the tumorigenic phenotype expressed by Madin-Darby canine kidney cells. Comp Med 61(3):243\u2013250","journal-title":"Comp Med"},{"issue":"1","key":"2625_CR19","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/ki.1994.6","volume":"45","author":"MJ Ryan","year":"1994","unstructured":"Ryan MJ et al (1994) HK-2: an immortalized proximal tubule epithelial cell line from normal adult human kidney. Kidney Int 45(1):48\u201357","journal-title":"Kidney Int"},{"issue":"1","key":"2625_CR20","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1099\/0022-1317-36-1-59","volume":"36","author":"FL Graham","year":"1977","unstructured":"Graham FL et al (1977) Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 36(1):59\u201372","journal-title":"J Gen Virol"},{"issue":"1-2","key":"2625_CR21","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ymgme.2019.05.015","volume":"128","author":"HL Runolfsdottir","year":"2019","unstructured":"Runolfsdottir HL et al (2019) Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects. Mol Genet Metab 128(1\u20132):144\u2013150","journal-title":"Mol Genet Metab"},{"key":"2625_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109557","volume":"345","author":"P Peerapen","year":"2021","unstructured":"Peerapen P, Thongboonkerd V (2021) Calcium oxalate monohydrate crystal disrupts tight junction via F-actin reorganization. Chem Biol Interact 345:109557","journal-title":"Chem Biol Interact"},{"issue":"1","key":"2625_CR23","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00011-013-0678-0","volume":"63","author":"L Guo","year":"2014","unstructured":"Guo L et al (2014) Role of Angptl4 in vascular permeability and inflammation. Inflamm Res 63(1):13\u201322","journal-title":"Inflamm Res"},{"issue":"49","key":"2625_CR24","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn6068","volume":"10","author":"SP Srivastava","year":"2024","unstructured":"Srivastava SP et al (2024) Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney disease. Sci Adv 10(49):eadn6068","journal-title":"Sci Adv"},{"key":"2625_CR25","doi-asserted-by":"crossref","unstructured":"Jomova K et al (2023) Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol 97(10):2499\u20132574","DOI":"10.1007\/s00204-023-03562-9"},{"issue":"1","key":"2625_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166825","volume":"1870","author":"J Moellmann","year":"2024","unstructured":"Moellmann J et al (2024) 2,8-dihydroxyadenine-induced nephropathy causes hexosylceramide accumulation with increased mTOR signaling, reduced levels of protective SirT3 expression and impaired renal mitochondrial function. Biochimica et Biophysica Acta (BBA) 1870(1):166825","journal-title":"Biochimica et Biophysica Acta (BBA)"},{"issue":"2","key":"2625_CR27","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1080\/21655979.2021.2012622","volume":"13","author":"L Yan","year":"2022","unstructured":"Yan L, Chen J, Fang W (2022) Exosomes derived from calcium oxalate-treated macrophages promote apoptosis of HK-2 cells by promoting autophagy. Bioengineered 13(2):2442\u20132450","journal-title":"Bioengineered"},{"key":"2625_CR28","doi-asserted-by":"crossref","unstructured":"Verhulst A et al (2003) Crystal retention capacity of cells in the human nephron: involvement of CD44 and its ligands hyaluronic acid and osteopontin in the transition of a crystal binding- into a nonadherent epithelium.\u00a0Am Soc Nephrol 13:107\u2013115","DOI":"10.1097\/01.ASN.0000038686.17715.42"},{"issue":"9","key":"2625_CR29","doi-asserted-by":"publisher","first-page":"5357","DOI":"10.1074\/jbc.M113.529313","volume":"289","author":"M Tsuneki","year":"2014","unstructured":"Tsuneki M, Madri JA (2014) CD44 regulation of endothelial cell proliferation and apoptosis via modulation of CD31 and VE-cadherin expression. J Biol Chem 289(9):5357\u20135370","journal-title":"J Biol Chem"},{"key":"2625_CR30","doi-asserted-by":"crossref","unstructured":"Loftus LV, Amend SR, Pienta KJ (2022) Interplay between cell death and cell proliferation reveals new strategies for cancer therapy.\u00a0Int J Mol Sci 23(9):4723","DOI":"10.3390\/ijms23094723"},{"issue":"1","key":"2625_CR31","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1186\/s13287-023-03571-6","volume":"14","author":"R Farahzadi","year":"2023","unstructured":"Farahzadi R et al (2023) Oxidative stress regulation and related metabolic pathways in epithelial\u2013mesenchymal transition of breast cancer stem cells. Stem Cell Res Ther 14(1):342","journal-title":"Stem Cell Res Ther"},{"issue":"33","key":"2625_CR32","doi-asserted-by":"publisher","first-page":"24477","DOI":"10.1074\/jbc.M702877200","volume":"282","author":"GW Prager","year":"2007","unstructured":"Prager GW et al (2007) CD98hc (SLC3A2) interaction with the integrin beta subunit cytoplasmic domain mediates adhesive signaling. J Biol Chem 282(33):24477\u201384","journal-title":"J Biol Chem"},{"issue":"4","key":"2625_CR33","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.ymgme.2004.05.004","volume":"82","author":"SC Elbein","year":"2004","unstructured":"Elbein SC et al (2004) Molecular screening of the human glutamine\u2013fructose-6-phosphate amidotransferase 1 (GFPT1) gene and association studies with diabetes and diabetic nephropathy. Mol Genet Metab 82(4):321\u2013328","journal-title":"Mol Genet Metab"},{"issue":"1","key":"2625_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00728-8","volume":"6","author":"J Kang","year":"2021","unstructured":"Kang J et al (2021) Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy. Signal Transduct Target Ther 6(1):323","journal-title":"Signal Transduct Target Ther"},{"issue":"45","key":"2625_CR35","doi-asserted-by":"publisher","first-page":"43377","DOI":"10.1074\/jbc.M206373200","volume":"277","author":"Gy Nowak","year":"2002","unstructured":"Nowak Gy (2002) Protein kinase C-\u03b1 and ERK1\/2 mediate mitochondrial dysfunction, decreases in active Na+ transport, and cisplatin-induced apoptosis in renal cells*. J Biol Chem 277(45):43377\u201343388","journal-title":"J Biol Chem"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-025-02625-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-025-02625-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-025-02625-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T21:19:35Z","timestamp":1767734375000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-025-02625-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["2625"],"URL":"https:\/\/doi.org\/10.1007\/s00109-025-02625-x","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]},"assertion":[{"value":"6 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"23"}}