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Molecular mechanisms underlying SS remain insufficiently defined. This study used four-dimensional DIA proteomics on tape-stripped stratum corneum from 30 SS and 30 nonsensitive skin subjects to map proteomic changes tied to barrier disruption, oxidative stress, and neuroinflammatory signaling.",{"@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":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/a-systemic-pathophysiological-view-of-sensitive-skin-revealed-by-proteomics-beyond-barrier-and-inflammation/458246/",{"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/a-systemic-pathophysiological-view-of-sensitive-skin-revealed-by-proteomics-beyond-barrier-and-inflammation/458246.png","ImageObject",300,407,{"name":92,"@type":93},"Jake","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main goal of the proteomics study on sensitive skin?","Question",{"text":112,"@type":113},"To characterize molecular alterations in sensitive skin versus nonsensitive skin and uncover key pathways involved in barrier dysfunction, oxidative stress, and neuroinflammatory responses.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were samples collected and analyzed in the study?",{"text":117,"@type":113},"Stratum corneum samples were collected using tape stripping from 30 subjects with sensitive skin and 30 with nonsensitive skin, then analyzed using four-dimensional data-independent acquisition (DIA) proteomics.",{"name":119,"@type":110,"acceptedAnswer":120},"Which biological pathways were most notably associated with sensitive skin results?",{"text":121,"@type":113},"Sensitive skin showed enrichment in cytoskeletal remodeling, cell–cell adhesion, and tight junction organization, along with increased oxidative phosphorylation and fatty acid β-oxidation, altered redox balance, and upregulated MAPK signaling and neurotrophin-related neuro-inflammatory pathways.","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},458246,1790797173,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Journal of Cosmetic Dermatology  \nORIGINAL ARTICLE  OPEN ACCESS   \nA Systemic Pathophysiological View of Sensitive Skin  \nRevealed by Proteomics: Beyond Barrier and Inflammation  \nLin Guihua  | Du Shan | Zhong Xinqing | Lee Yunha | Xiong Zhi Amorepacific (Shanghai) D&I Center Co. Ltd, Shanghai, People's Republic of China Correspondence: Xiong Zhi ([xiongzhi@cn.amorepacific.com](xiongzhi@cn.amorepacific.com))  \nReceived: 16 October 2025 | Revised: 16 December 2025 | Accepted: 19 December 2025  \nKeywords: nonsensitive skin | oxidative stress | proteomics | sensitive skin | skin barrier  \nABSTRACT  \nBackground: Sensitive skin (SS) is a common dermatological condition characterized by enhanced reactivity to environmental, chemical, and cosmetic stimuli, often accompanied by impaired barrier function and discomfort sensation such as burning or itching. Despite its high prevalence, the molecular mechanism underlying SS remains poorly understood.  \nObjectives: This study aimed to perform a comprehensive proteomics analysis to characterize molecular alterations in SS compared with nonsensitive skin (NS), thereby uncovering key pathways involved in barrier dysfunction, oxidative stress, and neuroinflammatory responses.  \nMethod: Thirty subjects with SS and 30 with NS were recruited. Stratum corneum samples were collected via tape stripping and analyzed using four-dimensional data-independent acquisition (DIA) proteomics.  \nResults: Proteomic profiling revealed distinct molecular signatures between SS and NS. SS exhibited enrichment of pathways related to cytoskeletal remodeling, cell–cell adhesion, and tight junction organization, consistent with impaired but dynamically compensatory barrier regulation. Enhanced oxidative phosphorylation and fatty acid β-oxidation indicated increased metabolic activity, while elevated glutathione-related enzyme functions reflected altered redox balance and oxidative stress. Additionally, upregulation of MAPK signaling and neurotrophin-associated pathways suggested active neuro-inflammatory crosstalk, potentially contributing to heightened cutaneous sensitivity and inflammatory susceptibility. Additional alterations were observed in other cellular processes, reflecting the complex molecular landscape of SS.  \nConclusion: These findings provide new insights into the molecular basis of SS, highlighting the interplay between barrier dysfunction, oxidative stress, and neuronal activation. The identified proteins and pathways may serve as potential biomarkers for SS assessment and as targets for the development of cosmetic products or therapeutic strategies aimed at restoring skin homeostasis.  \n1 | Introduction  \nSensitive skin (SS) represents a multifaceted condition characterized by heightened cutaneous reactivity to various stimuli. The diagnosis and clinical evaluation of SS syndrome can be effectively supported by a range of specialized sensory testing protocols. These include chemical provocation tests utilizing lactic acid, capsaicin, or dimethyl sulfoxide to assess stinging response; physical challenge methods such as occlusive patch  \ntesting and behind-the-knee tests; mechanical stimulation procedures, including controlled washing and exaggerated immersion tests [1] .  \nSeveral studies have suggested a link between SS and a disruption of the epidermal barrier function. SS is known to cause a noticeably decreased amount of neutral lipids and upregulated levels of sphingolipids that have been linked to reduced barrier stability [2] . An impaired skin barrier function compromises  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2026 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.  \nJournal of Cosmetic Dermatology, 2026; 25:e70649 1 of 16  \n[https://doi.org/10.1111/jocd.70649](https://doi.org/10.1111/jocd.70649","cbCaif98yfzkcIpL","https://ap.wps.com/l/cbCaif98yfzkcIpL","pdf",3262533,16,"English","# Introduction\n## Sensitive skin overview and evaluation\n## Background links to barrier dysfunction and oxidative stress\n# Methods\n## Study subjects and sample collection\n## DIA proteomics workflow","[{\"question\":\"What is the main goal of the proteomics study on sensitive skin?\",\"answer\":\"To characterize molecular alterations in sensitive skin versus nonsensitive skin and uncover key pathways involved in barrier dysfunction, oxidative stress, and neuroinflammatory responses.\"},{\"question\":\"How were samples collected and analyzed in the study?\",\"answer\":\"Stratum corneum samples were collected using tape stripping from 30 subjects with sensitive skin and 30 with nonsensitive skin, then analyzed using four-dimensional data-independent acquisition (DIA) proteomics.\"},{\"question\":\"Which biological pathways were most notably associated with sensitive skin results?\",\"answer\":\"Sensitive skin showed enrichment in cytoskeletal remodeling, cell–cell adhesion, and tight junction organization, along with increased oxidative phosphorylation and fatty acid β-oxidation, altered redox balance, and upregulated MAPK signaling and neurotrophin-related neuro-inflammatory pathways.\"}]","A Systemic Pathophysiological View of Sensitive Skin Revealed by Proteomics - Beyond Barrier and Inflammation | PDF",1790752322]