[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-455607-105":59,"doc-detail-455607-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","inhibition-of-fxiia-attenuates-kidney-fibrosis-in-mice-with-unilateral-ureteral-obstruction","Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction","","Kidney fibrosis is a hallmark of chronic kidney diseases, with parenchymal scarring predicting functional decline. Because contact-phase system activation and factor XII (FXII) may promote renal fibrosis, FXII inhibition with an anti-FXII/activated FXII antibody (3F7) was tested in unilateral ureteral obstruction (UUO). 3F7 preserved tissue architecture, reduced collagen deposition and apoptosis, and increased tubular epithelial proliferation. C1 esterase inhibitor showed no effect. Transcriptomics indicated dominant impact on stress-activated kinase signaling in response to DNA damage. FXII/FXIIa induced p21 via Akt and ERK1/2; 3F7 reduced p21+ epithelial cells, supporting a protective mechanism for chronic kidney injury.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/inhibition-of-fxiia-attenuates-kidney-fibrosis-in-mice-with-unilateral-ureteral-obstruction/455607/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/inhibition-of-fxiia-attenuates-kidney-fibrosis-in-mice-with-unilateral-ureteral-obstruction/455607.png","ImageObject",300,407,{"name":92,"@type":93},"Ezra","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-08","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main hypothesis behind using FXII inhibition in this study?","Question",{"text":112,"@type":113},"The study hypothesized that inhibiting FXII/activated FXII would reduce renal fibrosis, based on links between contact-phase system activation, FXII biology, and fibrotic processes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did 3F7 treatment affect kidney fibrosis in UUO mice?",{"text":117,"@type":113},"3F7 attenuated fibrosis by preserving tissue structure, decreasing collagen deposition, and reducing apoptosis, while increasing proliferation of tubular epithelial cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What molecular pathways and cellular markers were implicated in the mechanism?",{"text":121,"@type":113},"Transcriptome analysis highlighted stress-activated protein kinase signaling related to DNA damage responses. In renal epithelial cells, FXII/FXIIa triggered p21 expression through Akt and ERK1/2, and 3F7 lowered the number of p21+ tubular epithelial cells.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},455607,1791249766,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},1099514068035,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Cellular and Molecular Life Sciences (2026) 83:21  \n[https://doi.org/10.1007/s00018-025-05988-z](https://doi.org/10.1007/s00018-025-05988-z) Cellular and Molecular Life Sciences  \nORIGINAL ARTICLE  \nInhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction  \nDaniel Kalina1 · Daniel P. Potaczek2,3 · Jinyang Zeng-Brouwers4 · Mario Boehm1 · Marc W. Nolte1 · Maximilian Bielohuby1 · Ralph T. Schermuly5,6 · Liliana Schaefer4 · MalgorzataWygrecka1,2,5,6  \nReceived: 16 May 2025 / Revised: 27 October 2025 / Accepted: 6 November 2025 © The Author(s) 2025  \nAbstract  \nKidney fibrosis is a common manifestation of chronic kidney diseases, with parenchymal tissue scarring serving as ahistologic predictor of functional deterioration. Considering the relationships between contact-phase system activation and renal fibrosis as well as potential direct profibrotic activities of factor XII (FXII), we hypothesized that FXII inhibition with an anti-FXII/activated FXII (FXIIa) antibody (3F7) demonstrates therapeutic efficacy in a mouse model of unilateral ureteral obstruction (UUO) . Treatment of UUO mice with 3F7 attenuated kidney fibrosis, as evidenced by preserved tissue structure, decreased deposition of collagen, and diminished apoptosis, but increased proliferation of tubular epithelial cells. No effect was observed with the administration of C1 esterase inhibitor, which serves as a primary plasma inhibitor of FXIIa and kallikrein. Transcriptome analysis revealed that 3F7 therapy predominantly affects stress-activated protein kinase signaling cascades and signal transduction in response to DNA damage. Exposure of renal epithelial cells to FXII or FXIIa triggered p21 expression in an Akt-and ERK1/2-dependent manner. Accordingly, treatment of UUO mice with 3F7 reduced numbers of p21+ renal tubular epithelial cells. Our work provides proof-of-concept data supporting efficacy of 3F7 in the UUO model and unravels molecular mechanisms underlying the protective role ofFXII inhibition in chronic kidney injury.  \nKeywords Factor XII · Senescence · Epithelial cells · Kidney fibrosis  \nAbbreviations  \n􀀍 Malgorzata Wygrecka[malgorzata.wygrecka@innere.med.uni-giessen.de](malgorzata.wygrecka@innere.med.uni-giessen.de)  \n1 CSL Innovation GmbH, Marburg, Germany  \n2 Center for Infection and Genomics ofthe Lung (CIGL), Faculty of Medicine, Justus Liebig University (JLU), Universities of Giessen and Marburg Lung Center, Aulweg 132, 35392 Giessen, Germany  \n3 Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps-University Marburg, Marburg, Germany  \n4 Institute of Pharmacology and Toxicology, Goethe University, Frankfurt, Germany  \n5 Department of Internal Medicine, Member of the German Center for Lung Research, Justus Liebig University of Giessen, Giessen, Germany  \n6 Institute for Lung Health (ILH), Justus Liebig University (JLU), Giessen, Germany  \nα-SMA ARB  \nBK  \nBSAC1INHCD  \nCKD  \nCTR  \nDKD  \nDMEM  \nECM  \nEGFR  \nFCS  \nFNFXII(a) GEO GLP-1 RAGSEA  \nHEK  \nα-smooth muscle actin Angiotensin II receptor blockers Bradykinin  \nBovine serum albumin C1 esterase Inhibitor Catalytically dead Chronic kidney disease Control  \nDiabetic kidney disease Dulbecco’s modified eagle medium Extracellular matrix  \nEpidermal growth factor receptor Fetal calf Serum  \nFibronectin  \n(Activated) factor XII Gene expression omnibus  \nGlucagon-like peptide 1 receptor agonist Gene set enrichment analysis  \nHuman embryonic kidney  \n1 3  \nHRPTEpC KH KIM-1 ORA  \nPFA  \nPAS  \nRES  \nRLMSGLT2i TECs  \nuPAR  \nUUO  \nHuman renal proximal tubular epithelial cells Kidney tissue homogenates  \nKidney injury molecule-1  \nOverrepresentation analysis Paraformaldehyde Periodic acid-schiff Running enrichment score Ranked list metric  \nSodium glucose cotransporter 2 inhibitor  \nTubular epithelial cells Urokinase receptor Unilateral ureteral obstruction  \nIntroduction  \nMore than 1 in 7 US adults (about 35.5 million ","cbCaim290QGbxTzx","https://ap.wps.com/l/cbCaim290QGbxTzx","pdf",6015499,"English","# Abstract\n## Keywords\n## Abbreviations\n# Introduction\n## Chronic kidney disease prevalence and unmet therapies\n## Tubular epithelial cell loss and maladaptive remodeling\n## Hypercoagulability and coagulation-driven renal pathology","[{\"question\":\"What was the main hypothesis behind using FXII inhibition in this study?\",\"answer\":\"The study hypothesized that inhibiting FXII/activated FXII would reduce renal fibrosis, based on links between contact-phase system activation, FXII biology, and fibrotic processes.\"},{\"question\":\"How did 3F7 treatment affect kidney fibrosis in UUO mice?\",\"answer\":\"3F7 attenuated fibrosis by preserving tissue structure, decreasing collagen deposition, and reducing apoptosis, while increasing proliferation of tubular epithelial cells.\"},{\"question\":\"What molecular pathways and cellular markers were implicated in the mechanism?\",\"answer\":\"Transcriptome analysis highlighted stress-activated protein kinase signaling related to DNA damage responses. In renal epithelial cells, FXII/FXIIa triggered p21 expression through Akt and ERK1/2, and 3F7 lowered the number of p21+ tubular epithelial cells.\"}]","Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction | PDF",1790743592,48]