{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:00:19Z","timestamp":1790744419235,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304048"],"award-info":[{"award-number":["82304048"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2019A1515110109"],"award-info":[{"award-number":["2019A1515110109"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515012464"],"award-info":[{"award-number":["2025A1515012464"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    : Primary localized cutaneous amyloidosis (PLCA) is characterized by the deposition of amyloid material within the superficial dermis. Its origin and composition remain debated, including whether deposits derive from keratin filament degeneration or misfolded protein aggregation, and whether non\u2010protein components contribute.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objectives<\/jats:bold>\n                    : This study aimed to re\u2010examine the composition of PLCA deposits and elucidate how\n                    <jats:italic>OSMR<\/jats:italic>\n                    mutations drive their formation, focusing on protein aggregation and lipid metabolism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : We employed PROTEOSTAT staining, lipidomics, and Nile Red\/Oil Red O staining in patient tissues, engineered HaCaT cells, and mouse models, together with mechanistic functional analyses.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : PLCA lesions contain abundant protein aggregates alongside significant lipid accumulation, indicating pathological protein\u2013lipid complexes. As the common genetic defect in familial PLCA, OSMR\u03b2 deficiency significantly promoted both lipid accumulation and protein aggregation in cellular and animal models. Lipidomic profiling revealed alterations in unsaturated fatty acids (UFAs, C18:1\/C18:2) and ceramides. Crucially, exogenous UFAs induced protein aggregation. Mechanistically, OSMR\u03b2 deficiency impairs STAT5 activation, leading to AKR1B10 upregulation and lipid dysregulation, whereas inhibition of this axis rescued both phenotypes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    :\n                    <jats:italic>OSMR<\/jats:italic>\n                    mutation drives amyloid deposition in PLCA through a STAT5\u2013AKR1B10 lipid metabolic axis that promotes co\u2010aggregation of lipids and misfolded proteins, providing potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1002\/advs.78068","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:41:31Z","timestamp":1790743291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid Metabolic Dysregulation Driven by\n                    <i>OSMR<\/i>\n                    Mutations Underlies Amyloidogenesis in Primary Localized Cutaneous Amyloidosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8406-4623","authenticated-orcid":false,"given":"Huiting","family":"Liu","sequence":"first","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"},{"name":"The First School of Clinical Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-208X","authenticated-orcid":false,"given":"Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"},{"name":"The First School of Clinical Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"},{"name":"The First School of Clinical Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3787-4495","authenticated-orcid":false,"given":"Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-5379","authenticated-orcid":false,"given":"Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5275-2656","authenticated-orcid":false,"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7155-6079","authenticated-orcid":false,"given":"Bin","family":"Yang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou 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