[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-458511-105":59,"doc-detail-458511-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","atf3-aggravates-kidney-fibrosis-via-hdac6-dependent-epigenetic-reprogramming","ATF3 aggravates kidney fibrosis via HDAC6-dependent epigenetic reprogramming","","Kidney fibrosis is a common pathology and terminal stage of chronic kidney disease, and defining its mechanisms is essential for effective intervention. Activating transcription factors are linked to kidney disorders, yet their specific contribution to fibrosis is insufficiently characterized. By unbiased analysis of single-cell and bulk RNA sequencing, ATF3 was identified as highly upregulated in damaged tubular epithelial cells. ATF3 deletion in mice attenuated fibrosis and reduced fibrotic traits. Mechanistically, ATF3 recruited HDAC6 to the SMAD7 promoter, decreased H3K14 acetylation, suppressed SMAD7 transcription, and activated TGF-β/Smad3 signaling, worsening fibrosis.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/atf3-aggravates-kidney-fibrosis-via-hdac6-dependent-epigenetic-reprogramming/458511/",{"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/atf3-aggravates-kidney-fibrosis-via-hdac6-dependent-epigenetic-reprogramming/458511.png","ImageObject",300,407,{"name":92,"@type":93},"Terk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does ATF3 play in kidney fibrosis?","Question",{"text":113,"@type":114},"ATF3 is markedly upregulated in damaged tubular epithelial cells and promotes fibrotic remodeling. ATF3 deletion in mice attenuates kidney fibrosis and suppresses fibrotic traits in injured cells.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does ATF3 influence epigenetic regulation in this study?",{"text":118,"@type":114},"ATF3 recruits HDAC6 to the SMAD7 promoter. This reduces histone H3K14 acetylation and diminishes SMAD7 transcriptional activity.",{"name":120,"@type":111,"acceptedAnswer":121},"Which signaling pathway is activated downstream of ATF3-HDAC6?",{"text":122,"@type":114},"Suppression of SMAD7 triggers activation of the TGF-β/Smad3 pathway, which accelerates kidney fibrosis.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},458511,1790805930,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},1099525198933,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Ivyspring  \nInternational Publisher  \nInternationalJournal of Biological Sciences  \n2026; 22(2): 841-857. doi: 10.7150/ijbs.125062  \nResearch Paper  \nATF3 aggravates kidney fibrosis via HDAC6-dependent epigenetic reprogramming  \nSibei Tao1, Chenzhou Wu2, Fanyuan Yu2, Lina Yang1, Lingzhi Li1, Fan Guo1, Ting Xiang1, Liang Ma1,􀀍, Ping Fu1,􀀍  \n1. Division of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.  \n2. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.  \n􀀍 Corresponding authors: Liang Ma and Ping Fu. Email: [liang_m@scu.edu.cn](liang_m@scu.edu.cn) (L. Ma), [and fupinghx@scu.edu.cn](and fupinghx@scu.edu.cn) (P. Fu) .  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2025.09.11; Accepted: 2025.11.12; Published: 2026.01.01  \nAbstract  \nKidney fibrosis is the most common pathology and endpoint of CKD. Unraveling the mechanisms of kidney fibrosis is crucial. Activating transcription factors (ATFs) are implicated in a range of kidney diseases, but their roles in kidney fibrosis remain underexplored. In our investigation, employing an unbiased screening of ATF expression in fibrotic kidneys via analyzing single-cell and bulk RNA sequencing, we identified that ATF3 as the key player, markedly upregulated in damaged tubular epithelial cells (TECs) . Crucially, ATF3 deletion in mice markedly attenuated kidney fibrosis and abrogated fibrotic traits in injured TECs. At the molecular level, ATF3 was found to recruit HDAC6 to the SMAD7 promoter, eradicating histone 3 lysine 14 acetylation (H3K14ac) and diminishing SMAD7 transcription. This interaction between ATF3 and HDAC6 culminated in the suppression of Smad7, triggering the TGF-β/Smad3 pathway and exacerbating kidney fibrosis. Collectively, our findings shed light on the complex underpinnings of kidney fibrosis and herald novel therapeutic targets for combating CKD.  \nKeywords: kidney fibrosis, ATF3, HDAC6, epigenetic reprogramming  \nIntroduction  \nApproximately 850 million patients worldwide suffer from chronic kidney disease (CKD), a syndrome characterized by the persistent and irreversible loss of kidney function [1] . CKD has become a global health crisis with increasing prevalence as well as high economic costs [2, 3] . Kidney fibrosis is the most common pathology and endpoint of CKD, resulting in end-stage kidney disease (ESKD) [4, 5] . Non-resolving inflammation is a major driving force in kidney fibrogenesis [6, 7], where multiple types of cells are involved in promoting scar formation and the progression of kidney fibrosis [8-11] . Unfortunately, therapeutic options for kidney fibrosis are lacking [12] due to the limited understanding of its pathogenesis. Thus, it is urgent to explore the mechanisms underlying kidney fibrosis for effective treatments.  \nActivating transcription factors (ATFs) are a group of basic leucine zipper (bZIP) transcription  \nfactors with numerous physiological functions [13] . Due to their extensive functions, ATFs have gained importance in many popular fields [14] . Increasing evidence has shown that ATFs are involved in various kidney diseases and expressed in various types of cells in response to different stimuli [15-20] . For example, ATF1 is activated by uremic toxins inendothelial cells [19] . ATF2 is upregulated in small cysts in autosomal dominant polycystic kidney disease [16], and ATF3 is elevated in acute kidney injury (AKI) [17] . ATF5 is induced in diabetic kidney disease [18] . Furthermore, ATF4 and ATF6, which are stimulated during endoplas","cbCaiiucLIkzx5wq","https://ap.wps.com/l/cbCaiiucLIkzx5wq","pdf",10463591,17,"English","# Abstract\n# Introduction\n# Materials and Methods\n## Animal experiments","[{\"question\":\"What role does ATF3 play in kidney fibrosis?\",\"answer\":\"ATF3 is markedly upregulated in damaged tubular epithelial cells and promotes fibrotic remodeling. ATF3 deletion in mice attenuates kidney fibrosis and suppresses fibrotic traits in injured cells.\"},{\"question\":\"How does ATF3 influence epigenetic regulation in this study?\",\"answer\":\"ATF3 recruits HDAC6 to the SMAD7 promoter. This reduces histone H3K14 acetylation and diminishes SMAD7 transcriptional activity.\"},{\"question\":\"Which signaling pathway is activated downstream of ATF3-HDAC6?\",\"answer\":\"Suppression of SMAD7 triggers activation of the TGF-β/Smad3 pathway, which accelerates kidney fibrosis.\"}]","ATF3 aggravates kidney fibrosis via HDAC6-dependent epigenetic reprogramming | PDF",1790753540,43]