{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:45:50Z","timestamp":1770813950337,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggable genome\u2010wide Mendelian randomization (MR) analysis using blood cis\u2010expression quantitative trait locus (eQTL) and HS genome\u2010wide association study (GWAS) data. Colocalization, transcriptomic validation, single\u2010cell RNA sequencing, and cell\u2013cell communication analyses were integrated to explore gene function and cell\u2010type specificity. We identified eight genes that showed significant associations with HS through MR analysis. Colocalization analysis further prioritized PSMA4 and MAST3 as the most promising druggable targets for HS. Specifically, PSMA4 (single nucleotide polymorphisms [SNPs]\u2009=\u200910; inverse\u2010variance weighted [IVW] OR\u2009=\u20091.912, 95% CI: 1.492\u20132.450,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001; PP.H4\u2009=\u20090.975) and MAST3 (SNPs\u2009=\u200915; IVW OR\u2009=\u20090.557, 95% CI: 0.453\u20130.686,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001; PP.H4\u2009=\u20090.832) exhibited strong statistical associations. Transcriptomic validation revealed that PSMA4 was upregulated and MAST3 was downregulated in HS lesions. Further single\u2010cell analysis revealed that PSMA4 was predominantly enriched in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and involved in pro\u2010inflammatory signaling, particularly the tumor necrosis factor (TNF) pathway. PSMA4 and MAST3 are potential therapeutic targets for HS. PSMA4 may promote inflammation via CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2010mediated signaling, offering a novel avenue for treatment development.\n                  <\/jats:p>","DOI":"10.1155\/mi\/4954996","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T05:45:12Z","timestamp":1770788712000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PSMA4 as a Druggable Target in Hidradenitis Suppurativa: Evidence From Mendelian Randomization and Single\u2010Cell Transcriptomics"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0686-7702","authenticated-orcid":false,"given":"Siqing","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4779-873X","authenticated-orcid":false,"given":"Lixin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7448-0324","authenticated-orcid":false,"given":"Peihong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0584-7780","authenticated-orcid":false,"given":"Boyun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9112-4372","authenticated-orcid":false,"given":"Jingen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.08.090"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16677"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13928"},{"key":"e_1_2_13_4_2","first-page":"15","article-title":"A 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