[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-450257-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-450257-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","28-dihydroxyadenine-disrupts-epithelial-integrity-and-alters-kidney-cell-phenotype-in-vitro-abstract","2,8-Dihydroxyadenine disrupts epithelial integrity and alters kidney cell phenotype in vitro - Abstract","","Adenine phosphoribosyltransferase (APRT) deficiency leads to urinary accumulation of 2,8-dihydroxyadenine (DHA), driving kidney stones and chronic kidney disease (CKD) that may progress to end-stage disease without timely care. Xanthine oxidoreductase inhibitors allopurinol and febuxostat block DHA generation and can halt or delay stone formation and CKD progression, though some patients cannot tolerate them. This study examines DHA effects on HK-2, HEK293, and MDCK kidney cells, showing reduced viability and impaired migration, altered epithelial barrier integrity, and RNA-seq changes linked to inflammation, mTORC1 signaling, and EMT suppression.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/28-dihydroxyadenine-disrupts-epithelial-integrity-and-alters-kidney-cell-phenotype-in-vitro-abstract/450257/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/28-dihydroxyadenine-disrupts-epithelial-integrity-and-alters-kidney-cell-phenotype-in-vitro-abstract/450257.png","ImageObject",300,407,{"name":42,"@type":43},"Miles","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-07","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":33},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What condition is studied and what does it cause?","Question",{"text":62,"@type":63},"APRT deficiency is an autosomal recessive disorder that causes accumulation of 2,8-dihydroxyadenine (DHA) in the urinary tract, leading to kidney stones and chronic kidney disease (CKD).","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How does DHA affect cultured kidney cells in vitro?",{"text":67,"@type":63},"DHA exposure reduces cell viability and impairs migration across HK-2, HEK293, and MDCK cells. In MDCK cells it also lowers epithelial integrity based on TEER measurements.",{"name":69,"@type":60,"acceptedAnswer":70},"Which molecular pathways and markers change after DHA treatment?",{"text":71,"@type":63},"RNA sequencing in DHA-treated HK-2 cells shows upregulation of TNF-α and mTORC1 signaling and downregulation of epithelial to mesenchymal transition and oxidative phosphorylation, with enrichment in inflammation, metabolic, and cell-cycle related pathways.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},450257,1790768415,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":33,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Journal of Molecular Medicine (2026) 104:23 [https://doi.org/10.1007/s00109-025-02625-x](https://doi.org/10.1007/s00109-025-02625-x)  \n2,8‑Dihydroxyadenine disrupts epithelial integrity and alters kidney cell phenotype in vitro  \nHildur Run Helgudottir1 · Runolfur Palsson1,2 · Vidar Orn Edvardsson1,3 · Thorarinn Gudjonsson1,4  \nReceived: 6 May 2025 / Revised: 14 October 2025 / Accepted: 19 October 2025 © The Author(s) 2026  \nAbstract  \nAdenine phosphoribosyltransferase (APRT) deficiency is an autosomal recessive disorder that causes accumulation of 2,8-dihydroxyadenine (DHA) in the urinary tract, leading to kidney stones and chronic kidney disease (CKD) . Progression to end-stage kidney disease can occur without timely treatment. The xanthine oxidoreductase inhibitors, allopurinol and febuxostat, block DHA generation and halt or delay stone formation and CKD progression. Some patients do not tolerate xanthine oxidoreductase inhibitor treatment, necessitating new therapeutic approaches. This study aimed to investigate how DHA influences structural and molecular changes in HK-2, HEK293, and MDCK kidney cells. DHA exposure reduced cell viability and impaired migration in all cell lines. Increased expression of the adhesion protein CD44 was observed adjacent to DHA crystals in HEK293 and HK-2 cells. Transepithelial electrical resistance measurements in MDCK cells indicated reduced epithelial integrity following DHA exposure. RNA sequencing of DHA-treated HK-2 cells revealed gene expression changes, with upregulation ofTNF-α and mTORC1 signaling and downregulation of epithelial to mesenchymal transition and oxidative phosphorylation. Functional enrichment analysis highlighted pathways related to cell cycle regulation, inflammation, and metabolic processes. These findings show that dose-dependent DHA toxicity interrupts cell migration and epithelial integrity. CD44 may contribute to crystal adhesion, and thus, represents a potential therapeutic target in DHA crystal nephropathy.  \nKey messages  \n• DHA reduces kidney cell viability and migration in a dose-dependent manner.  \n• DHA disrupts epithelial integrity in MDCK cells, lowering TEER values.  \n• CD44 expression increases adjacent to DHA crystals with increased DHA concentration.  \n• RNA sequencing shows that DHA upregulates TNF-α, mTORC1, and stress pathways.  \n• DHA alters gene expression, affecting inflammation, metabolism, and EMT.  \nKeywords APRT deficiency · CD44 · RNA sequencing · Cell viability · Epithelial barrier integrity  \n* Hildur Run Helgudottir [hrh@hi.is](hrh@hi.is)  \nThorarinn Gudjonsson  \n[tgudjons@hi.is](tgudjons@hi.is)  \n1 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland  \n2 Section of Nephrology, Landspitali University Hospital, Reykjavik, Iceland  \n3 Children’s Medical Center, Landspitali University Hospital, Reykjavik, Iceland  \n4 Section of Laboratory Hematology, Landspitali University Hospital, Reykjavik, Iceland  \nIntroduction  \nAdenine phosphoribosyltransferase (APRT) deficiency (OMIM102600) is a rare autosomal recessive disorder of adenine metabolism that results in the urinary excretion of large amounts of the poorly soluble When dividing 2,8-dihydroxyadenine (DHA) between lines use: 2,8-dihydroxy-adenine (DHA) causing urinary tract stone formation, crystal nephropathy, and progressive chronic kidney disease (CKD) [1–3] . The xanthine oxidoreductase (XOR) inhibitors, allopurinol and/ or febuxostat, are readily available treatment options that effectively prevent stone formation and CKD progression inpatients with APRT deficiency by blocking the conversion  \nof adenine to DHA [1–3] . Unfortunately, some affected individuals tolerate neither allopurinol nor febuxostat and, therefore, alternative treatment options are needed.  \nTraditionally, DHA crystal deposition in the kidneys has been assumed to cause direct mechanical tubular obstruction and nephron destruction, resulting in progressive CKD [2] . Recent studi","cbCaitPIxYUX4oil","https://ap.wps.com/l/cbCaitPIxYUX4oil","pdf",10147366,14,"English","# Abstract\n## Key messages\n## Introduction","[{\"question\":\"What condition is studied and what does it cause?\",\"answer\":\"APRT deficiency is an autosomal recessive disorder that causes accumulation of 2,8-dihydroxyadenine (DHA) in the urinary tract, leading to kidney stones and chronic kidney disease (CKD).\"},{\"question\":\"How does DHA affect cultured kidney cells in vitro?\",\"answer\":\"DHA exposure reduces cell viability and impairs migration across HK-2, HEK293, and MDCK cells. In MDCK cells it also lowers epithelial integrity based on TEER measurements.\"},{\"question\":\"Which molecular pathways and markers change after DHA treatment?\",\"answer\":\"RNA sequencing in DHA-treated HK-2 cells shows upregulation of TNF-α and mTORC1 signaling and downregulation of epithelial to mesenchymal transition and oxidative phosphorylation, with enrichment in inflammation, metabolic, and cell-cycle related pathways.\"}]","2,8-Dihydroxyadenine disrupts epithelial integrity and alters kidney cell phenotype in vitro - Abstract | PDF",1790732651,35]