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Using human single-cell RNA-seq and Ube4A global knockout mice with DSS-induced colitis, Ube4A loss worsened disease and altered inflammatory, lipid-handling, antimicrobial, and mast-cell programs, even at baseline.",{"@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/loss-of-e3-ligase-ube4a-disrupts-colon-homeostasis-and-accelerates-experimental-colitis-via-altered-lipid-handling/440614/",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/loss-of-e3-ligase-ube4a-disrupts-colon-homeostasis-and-accelerates-experimental-colitis-via-altered-lipid-handling/440614.png","ImageObject",300,407,{"name":42,"@type":43},"CatatanPagi","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",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 role does Ube4A play in intestinal homeostasis?","Question",{"text":62,"@type":63},"Ube4A helps maintain colon homeostasis, and its loss triggers epithelial stress and metabolic reprogramming. The study identifies Ube4A as a regulator whose deficiency sensitizes the colon to exaggerated inflammatory responses during injury.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How was Ube4A function investigated in the study?",{"text":67,"@type":63},"Human relevance was assessed using publicly available single-cell RNA-seq datasets comparing healthy and IBD tissues. Mouse mechanisms were tested using global Ube4A knockout mice subjected to DSS-induced colitis, followed by transcriptomic analyses, immunofluorescence, and flow cytometry.",{"name":69,"@type":60,"acceptedAnswer":70},"What changes occur in mice lacking Ube4A during DSS-induced colitis?",{"text":71,"@type":63},"Ube4A deficiency significantly exacerbated DSS colitis, with increased weight loss, higher disease activity scores, shortened colon length, and more severe histological injury. Transcriptomics showed heightened inflammatory signaling plus dysregulated lipid transport/storage, antimicrobial defenses, mast cell activation, and increased matrix metalloproteinases.","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},440614,1790710548,{"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},962090894170,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","bioRxiv preprint doi: [https://doi.org/10.64898/2026.01.02.697430](https://doi.org/10.64898/2026.01.02.697430); this version posted January 3, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-ND 4.0 International license.  \nLoss of E3 ligase Ube4A Disrupts Colon Homeostasis and Accelerates Experimental Colitis via Altered Lipid Handling  \nSimon Guignard 1, Molee Chakraborty 1,4, Silvia Gonzalez-Nieves 1, David DeBruin2, Emily Ebert3, Anastasiia Vinogradskaia 1, Michelle Brennan2, Ryan M Teague3, Anutosh  \nChakraborty 1,4,5*, Vincenza Cifarelli 1,5*  \n1Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri, USA. 2Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri, USA. 3Department of Molecular Biology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA. 4Current address: Department of Cellular and Systems Pharmacology, University of Florida College of Medicine, Gainesville, Florida, USA. 5 Senior authors contributed equally.  \nRunning Title: Ube4A deletion exacerbates colitis  \n*Correspondence: Vincenza Cifarelli, Ph.D.  \nDepartment of Pharmacology and Physiology  \nSaint Louis University School of Medicine  \n1402 South Grand Boulevard  \nSt. Louis, MO 63104  \nPhone: (314) 977-6419  \n[E-mail:](E-mail: vincenza.cifarelli@health.slu.edu)[ ](E-mail: vincenza.cifarelli@health.slu.edu)[vincenza.cifarelli@health.slu.edu](E-mail: vincenza.cifarelli@health.slu.edu)  \n[Anutosh Chakraborty](Anutosh Chakraborty), Ph.D.  \nDepartment of Cellular and Systems Pharmacology  \nUniversity of Florida College of Pharmacy  \n1345 Center Drive  \nGainesville, FL 32610  \nPhone: (352) 273-7517  \nE-mail: [anutoshchakrabor@ufl.edu](anutoshchakrabor@ufl.edu)  \nbioRxiv preprint doi: [https://doi.org/10.64898/2026.01.02.697430](https://doi.org/10.64898/2026.01.02.697430); this version posted January 3, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-ND 4.0 International license.  \nABSTRACT  \nBackground. Ubiquitin-dependent signaling is essential for maintaining intestinal homeostasis and its dysregulation contributes to chronic intestinal disorders, such as Inflammatory Bowel Disease (IBD) . Ube4A is a U-box E3/E4 ubiquitin ligase involved in lipid metabolism and insulin signaling in metabolic tissues. Autoantibodies against Ube4A have been identified in patients with IBD and are associated with disease long-term complications. Despite these clinical associations, the physiological role of Ube4A in the gastrointestinal tract remains unknown. This study aimed to define the function of Ube4A in the colon and determine how its loss influences susceptibility to experimental colitis. Methods. UBE4A expression in human colonic tissue from healthy individuals and patients with IBD was analyzed using publicly available single-cell RNA sequencing datasets. The role of Ube4A in colonic homeostasis and colitis pathogenesis was examined using global Ube4A knockout (UKO) mice subjected to dextran sulfate sodium (DSS) -induced colitis. UKO colon phenotypes were characterized using transcriptomic analyses, immunofluorescence, and flow cytometry. Results. UBE4A is highly expressed in human colonic epithelial cells, and its expression is reduced from healthy to IBD inflamed tissues. In mice, Ube4A deficiency significantly exacerbated DSS-induced colitis, as evidenced by increased weight loss, disease activity scores, shortened colon length, and more severe histological injury. Transcriptomic profiling revealed enhanced inflammatory signaling, alongside dysregulation of lipid transport and storage, as well","cbCaik4newbVGeO3","https://ap.wps.com/l/cbCaik4newbVGeO3","pdf",4998182,35,"English","# Abstract\n# Introduction\n## Methods\n## Results\n## Conclusions","[{\"question\":\"What role does Ube4A play in intestinal homeostasis?\",\"answer\":\"Ube4A helps maintain colon homeostasis, and its loss triggers epithelial stress and metabolic reprogramming. The study identifies Ube4A as a regulator whose deficiency sensitizes the colon to exaggerated inflammatory responses during injury.\"},{\"question\":\"How was Ube4A function investigated in the study?\",\"answer\":\"Human relevance was assessed using publicly available single-cell RNA-seq datasets comparing healthy and IBD tissues. Mouse mechanisms were tested using global Ube4A knockout mice subjected to DSS-induced colitis, followed by transcriptomic analyses, immunofluorescence, and flow cytometry.\"},{\"question\":\"What changes occur in mice lacking Ube4A during DSS-induced colitis?\",\"answer\":\"Ube4A deficiency significantly exacerbated DSS colitis, with increased weight loss, higher disease activity scores, shortened colon length, and more severe histological injury. Transcriptomics showed heightened inflammatory signaling plus dysregulated lipid transport/storage, antimicrobial defenses, mast cell activation, and increased matrix metalloproteinases.\"}]","Loss of E3 ligase Ube4A Disrupts Colon Homeostasis and Accelerates Experimental Colitis via Altered Lipid Handling | PDF",1790692687,88]