{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:50:06Z","timestamp":1786686606648,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Stevens\u2013Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of severe drug\u2010induced cutaneous reactions. These conditions are characterized by widespread and confluent keratinocyte apoptosis, which differentiates them from erythema multiforme (EM). Mounting evidence has implicated the mitochondrial\u2010dependent apoptosis pathway in the pathogenesis of SJS\/TEN, but the potential roles and specific mechanisms of these pathways in SJS\/TEN remain largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Proteomic analyses were conducted to investigate differential protein expression in blister fluid (BF)\u2010derived exosomes from suction surgery in healthy individuals (Con Exo) or patients with EM (EM Exo) or SJS\/TEN (TEN Exo). Further analysis involved glutathione S\u2010transferase (GST) pull\u2010down assay, liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) analysis, and validation of MS results through proximity ligation assay (PLA) and coimmunoprecipitation (co\u2010IP). Phenotypic and mechanistic analyses were performed using immunohistochemistry (IHC) staining, enzyme\u2010linked immunosorbent assay (ELISA), western blotting, reverse transcription\u2013polymerase chain reaction (RT\u2010PCR), co\u2010IP, CCK\u20108 assay, adenosine triphosphate (ATP) level measurements, and flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Galectin\u20107 was markedly upregulated in BF\u2010derived exosomes from SJS\/TEN patients and showed a correlation with disease severity. Further analysis confirmed the interaction between galectin\u20107 and transient receptor potential (melastatin) 2 (TRPM2). BF\u2010derived exosomes from SJS\/TEN patients induced an imbalance in mitochondrial dynamics via galectin\u20107\/TRPM2 upregulation. Activation of TRPM2 led to an elevation in mitochondrial Zn<jats:sup>2+<\/jats:sup>, which facilitated the recruitment of the fission factor dynamin\u2010related protein\u20101 (DRP\u20101) to mitochondria to trigger mitochondrial fission in the keratinocyte. In addition, the recruitment of DRP\u20101\u2010dependent mitochondrial fission via the voltage\u2010dependent anion channel 1 (VDAC1)\/hexokinase 2 (HK2)\u2010mediated opening of the mitochondrial permeability transition pore (mPTP)\u2010triggered cytochrome c release. These effects ultimately induce activation of the intrinsic mitochondrial apoptotic pathway and contribute to the pathogenesis of SJS\/TEN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Targeting the galectin\u20107\/TRPM2\/Zn<jats:sup>2+<\/jats:sup>\/DRP\u20101 signaling pathway in keratinocytes presents a prospective therapeutic strategy for mitigating SJS\/TEN in the future.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16510","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T09:37:06Z","timestamp":1741772226000},"page":"1358-1376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeting the Galectin\u20107\/<scp>TRPM2<\/scp>\/Zn<sup>2+<\/sup>\/<scp>DRP<\/scp>\u20101 Signaling Pathway: A Potential Therapeutic Intervention in the Pathogenesis of <scp>SJS<\/scp>\/<scp>TEN<\/scp>"],"prefix":"10.1111","volume":"80","author":[{"given":"Chen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology Xijing Hospital, Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BingYu","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital, Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YiXin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital, Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zipeng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Health Education and Management and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital, Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhenLai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital, Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital, Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JianKang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital, Fourth Military Medical University  Xi'an 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