[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-434079-105":59,"doc-detail-434079-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","keloids-as-a-spectrum-of-auto-inflammatory-fibrotic-disorders-beyond-the-conventional-wound-healing-paradigm","Keloids as a Spectrum of Auto-Inflammatory Fibrotic Disorders - Beyond the Conventional Wound-Healing Paradigm","","Keloids have traditionally been viewed as fibroproliferative disorders, yet accumulating evidence identifies chronic inflammation and immune dysregulation as the core pathogenic driver. This review reframes keloids as a spectrum of auto-inflammatory fibrotic diseases, integrating findings on genetic and epigenetic priming of hyperinflammation, amplification by endocrine influences, and execution through abnormal signaling. The inflammatory environment promotes fibroblast metabolic reprogramming toward a Warburg-like state, supporting persistent proliferation and ECM deposition. Coordinated immune cell infiltration and skewed polarization sustain a fibro-inflammatory cascade that explains recurrence and heterogeneity, informing mechanism-driven combination therapies targeting the inflammatory core and downstream metabolic consequences.",{"@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/keloids-as-a-spectrum-of-auto-inflammatory-fibrotic-disorders-beyond-the-conventional-wound-healing-paradigm/434079/",{"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/keloids-as-a-spectrum-of-auto-inflammatory-fibrotic-disorders-beyond-the-conventional-wound-healing-paradigm/434079.png","ImageObject",300,407,{"name":92,"@type":93},"Valentina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-07","2026-09-29",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},"How does this review redefine keloids compared with the conventional fibroproliferative model?","Question",{"text":113,"@type":114},"It reframes keloids as a spectrum of auto-inflammatory fibrotic disorders, placing chronic inflammation and immune dysregulation at the center of pathogenesis rather than treating inflammation as secondary.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What mechanisms are proposed to sustain pathological healing in keloids?",{"text":118,"@type":114},"Genetic predisposition and epigenetic changes prime a hyperinflammatory response, which is amplified by endocrine factors and propagated through aberrant signaling pathways. Immune cell infiltration and skewed polarization further fuel a fibro-inflammatory cascade.",{"name":120,"@type":111,"acceptedAnswer":121},"Why do current treatments often fail to prevent recurrence?",{"text":122,"@type":114},"Because keloids are driven by persistent, mechanism-based inflammatory and fibroblast pathways. Therapies used alone may not adequately target the inflammatory core and the downstream metabolic and ECM deposition processes that sustain disease.","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},434079,1790862542,{"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},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","Clinical, Cosmetic and Investigational Dermatology  \nOpen Access Full Text Article REVIEW  \nKeloids as a Spectrum of Auto-Inflammatory Fibrotic Disorders: Beyond the Conventional Wound-Healing Paradigm  \nNan Cao, Xiaoliang Xiong, Shan Liu, Weijian Kong, Yinlong Zhao  \nDepartment of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, People’s Republic of China  \nCorrespondence: Yinlong Zhao, Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, [Email yinlong@jlu.edu.cn](Email yinlong@jlu.edu.cn)  \n\n| Abstract: Keloids have traditionally been classified as fibroproliferative disorders; however, emerging evidence establishes chronic inflammation and immune dysregulation as the central pathogenic nexus, orchestrating a self-sustaining cycle of pathological healing. This review proposes a paradigm shift toward understanding keloids as a spectrum of auto-inflammatory fibrotic disorders. We synthesize recent advances to demonstrate how genetic predisposition and epigenetic modifications prime a hyperinflammatory response, which is then amplified by endocrine factors and executed through aberrant signaling pathways. Crucially, this inflammatory milieu drives the metabolic reprogramming of fibroblasts toward a Warburg-like phenotype, providing the bioenergetic and biosynthetic substrate for relentless proliferation and extracellular matrix (ECM) deposition. Infiltration and skewed polarization of immune cells further fuel this fibro-inflammatory cascade. Our integrative framework, positioning dysregulated immunity as the disease core, explains keloid persistence, recurrence, and heterogeneity, thereby providing a rationale for combination-based, mechanism-driven therapies. Ultimately, this perspective illuminates novel therapeutic strategies that target the inflammatory core (eg, biologic agents against Th2 cytokines and mast cell products) and its downstream consequences (eg, metabolic inhibitors), offering hope for more effective, mechanism-based interventions against this recalcitrant condition.\u003Cbr>Keywords: keloids, scar, inflammation, fibroblasts, genetic |\n| --- |\n| Introduction\u003Cbr>Keloids represent a unique form of pathological wound healing, characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix (ECM) deposition that arise beyond the boundaries of the original wound edges.1 In addition to causing visible scarring, these lesions frequently provoke symptoms such as persistent pruritus and tenderness. This contributes to a significant psychological burden, which is exacerbated when they occur on exposed body parts, such as the face.2–4 Epidemiological studies have demonstrated significant racial disparities in the prevalence of excessive scarring, with rates of 2.4% in Black, 1. 1% in Asian, and 0.4% in White populations.5 The majority of people afflicted with keloids are between the ages of 10 and 30 years.6 Multiple pathogenic contributors have been identified, including genetics, hormone levels,7 local skin tension,8 trauma, folliculitis, and lifestyle.9 Despite the widespread impact ofkeloids, current therapeutic options remain limited and sometimes unsatisfactory. Treatments such as surgical excision, corticosteroid injections, cryotherapy, laser therapy, and radiation are commonly employed. However, recurrence rates remain high, particularly when used alone. This clinical challenge underscores the urgent need for a deeper mechanistic understanding to guide the development of more effective and individualized treatment strategies.\u003Cbr>Current evidence suggests that keloid pathogenesis involves a complex interplay of immune dysregulation and chronic inflammation (Figure 1) . Key signaling pathways such as transforming growth factor (TGF)-β and integrin signaling have been implicated in the promotion of fibroblast activation and ECM deposition. However, their hierarchical relationships and spatiotemporal regula","cbCaikBG4q2B1Udw","https://ap.wps.com/l/cbCaikBG4q2B1Udw","pdf",2147267,15,"English","# Introduction\n## Current therapeutic challenges and need for mechanistic understanding\n## Immune dysregulation and chronic inflammation in keloid pathogenesis\n# Signaling pathways implicated in fibroblast activation and ECM deposition","[{\"question\":\"How does this review redefine keloids compared with the conventional fibroproliferative model?\",\"answer\":\"It reframes keloids as a spectrum of auto-inflammatory fibrotic disorders, placing chronic inflammation and immune dysregulation at the center of pathogenesis rather than treating inflammation as secondary.\"},{\"question\":\"What mechanisms are proposed to sustain pathological healing in keloids?\",\"answer\":\"Genetic predisposition and epigenetic changes prime a hyperinflammatory response, which is amplified by endocrine factors and propagated through aberrant signaling pathways. Immune cell infiltration and skewed polarization further fuel a fibro-inflammatory cascade.\"},{\"question\":\"Why do current treatments often fail to prevent recurrence?\",\"answer\":\"Because keloids are driven by persistent, mechanism-based inflammatory and fibroblast pathways. Therapies used alone may not adequately target the inflammatory core and the downstream metabolic and ECM deposition processes that sustain disease.\"}]","Keloids as a Spectrum of Auto-Inflammatory Fibrotic Disorders - Beyond the Conventional Wound-Healing Paradigm | PDF",1790666799,38]