{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:14:32Z","timestamp":1793218472372,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"publisher","award":["SUBK.C260.23.037"],"award-info":[{"award-number":["SUBK.C260.23.037"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Hidradenitis suppurativa (HS) is a debilitating inflammatory skin condition with unclear underlying mechanisms. Recent studies suggest pyroptosis, a highly inflammatory form of programmed cell death, could significantly contribute to the disease process. This study aimed to investigate the roles of gasdermin D (GSDMD) and gasdermin E (GSDME), two key mediators of pyroptosis, in HS pathogenesis. Serum and skin samples from HS patients and healthy individuals were analyzed. Serum gasdermin D levels were significantly elevated in HS patients, although gasdermin E showed no significant difference compared to controls. Skin tissue analysis revealed increased expression of both GSDMD and GSDME in inflamed HS lesions compared to unaffected skin from the same patients and healthy control skin. However, these molecules did not correlate directly with disease severity. Interestingly, systemic metabolic markers showed some associations with gasdermin expression, suggesting potential connections between systemic health and inflammation in HS. These findings confirm a critical role of gasdermins in HS-related inflammation and identify pyroptosis as a promising therapeutic target. Further exploration of these pathways could yield valuable treatment strategies for managing this challenging skin condition.<\/jats:p>","DOI":"10.3390\/biology14091258","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T12:08:16Z","timestamp":1757678896000},"page":"1258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gasdermin-Mediated Pyroptosis in Hidradenitis Suppurativa: Molecular Insights and Therapeutic Implications"],"prefix":"10.3390","volume":"14","author":[{"given":"Kinga","family":"Tyczy\u0144ska","sequence":"first","affiliation":[{"name":"Clinical Department of Rheumatology and Internal Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr K.","family":"Krajewski","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Venereology and Clincial Immunology, Faculty of Medicine, Wroclaw University of Science and Technology, 50-377 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3347-2472","authenticated-orcid":false,"given":"Aleksandra","family":"S\u00f3jka","sequence":"additional","affiliation":[{"name":"University Centre of General Dermatology and Oncodermatology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Nowicka-Suszko","sequence":"additional","affiliation":[{"name":"University Centre of General Dermatology and Oncodermatology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-2017","authenticated-orcid":false,"given":"Iwona","family":"Bednarz-Misa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-327X","authenticated-orcid":false,"given":"Mariusz","family":"Fleszar","sequence":"additional","affiliation":[{"name":"Omics Research Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Krzystek-Korpacka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-6342","authenticated-orcid":false,"given":"Jacek C.","family":"Szepietowski","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Venereology and Clincial Immunology, Faculty of Medicine, Wroclaw University of Science and Technology, 50-377 Wroclaw, Poland"},{"name":"Department of Dermato-Venereology, 4th Military Hospital, 50-981 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-020-0149-1","article-title":"Hidradenitis suppurativa","volume":"6","author":"Sabat","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Krajewski, P.K., Matusiak, \u0141., von Stebut, E., Schultheis, M., Kirschner, U., Nikolakis, G., and Szepietowski, J.C. (2021). Quality-of-Life Impairment among Patients with Hidradenitis Suppurativa: A Cross-Sectional Study of 1795 Patients. Life, 11.","DOI":"10.3390\/life11010034"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1111\/bjd.16603","article-title":"Profound consequences of hidradenitis suppurativa: A review","volume":"183","author":"Matusiak","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4400","DOI":"10.3390\/cimb45050280","article-title":"Hidradenitis Suppurativa: Molecular Etiology, Pathophysiology, and Management\u2014A Systematic Review","volume":"45","author":"Diaz","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1001\/jamadermatol.2023.2217","article-title":"Genetic Variants Associated With Hidradenitis Suppurativa","volume":"159","author":"Sun","year":"2023","journal-title":"JAMA Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s13555-023-01083-y","article-title":"An Atlas of the Hidradenitis Suppurativa Transcriptome","volume":"14","author":"Szukala","year":"2024","journal-title":"Dermatol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"167378","DOI":"10.1016\/j.jmb.2021.167378","article-title":"Apoptosis, Pyroptosis, and Necroptosis-Oh My! The Many Ways a Cell Can Die","volume":"434","author":"Fitzgerald","year":"2022","journal-title":"J. Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.mib.2013.04.004","article-title":"Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection","volume":"16","author":"Aachoui","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e98321","DOI":"10.15252\/embj.201798321","article-title":"Mechanism of membrane pore formation by human gasdermin-D","volume":"37","author":"Mulvihill","year":"2018","journal-title":"EMBO J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.15252\/embj.201694696","article-title":"GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death","volume":"35","author":"Sborgi","year":"2016","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"663","DOI":"10.3390\/cimb46010043","article-title":"Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review","volume":"46","author":"Krajewski","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_13","unstructured":"Roenigk, R., and Roenigk, H. (1989). Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: Surgical approach. Dermatologic Surgery, Marcel Dekker."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1111\/bjd.15748","article-title":"Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity","volume":"177","author":"Zouboulis","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_15","first-page":"395","article-title":"Concise Review of Common Non-Traditional Dyslipidemic Indices in Clinical Practice","volume":"6","author":"Khazaal","year":"2023","journal-title":"AlQalam J. Med. App. Sci."},{"key":"ref_16","unstructured":"Kennedy, S., and Oswald, N. (2011). qPCR data analysis\u2014Unlocking the secret to successful results. PCR Troubleshooting and Optimization: The Essential Guide, Caister Academic Press. [1st ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.semcdb.2022.01.006","article-title":"Advances in molecular pathogenesis of hidradenitis suppurativa: Dysregulated keratins and ECM signaling","volume":"128","author":"Kashyap","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/bjd\/ljad273","article-title":"Aberrant expression of interleukin-17A in mast cells contributes to the pathogenesis of hidradenitis suppurativa","volume":"189","author":"Chu","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1093\/bjd\/ljad274","article-title":"Spatial transcriptomic profiling reveals the pathophysiology of early-stage hidradenitis suppurativa","volume":"189","author":"Jeong","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Witte, K., Sabat, R., Witte-H\u00e4ndel, E., Ghoreschi, K., and Wolk, K. (2022). Phytotherapeuthics Affecting the IL-1\/IL-17\/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169057"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.it.2019.09.005","article-title":"Emerging Activators and Regulators of Inflammasomes and Pyroptosis","volume":"40","author":"Xue","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1084\/jem.20172060","article-title":"GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever","volume":"215","author":"Kanneganti","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e3000047","DOI":"10.1371\/journal.pbio.3000047","article-title":"Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice","volume":"16","author":"Xiao","year":"2018","journal-title":"PLoS Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0167-4889(00)00066-5","article-title":"Interleukin-1beta increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool","volume":"1497","author":"Hu","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"893912","DOI":"10.3389\/fimmu.2022.893912","article-title":"The Regulation and Modification of GSDMD Signaling in Diseases","volume":"13","author":"Li","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s13075-021-02580-1","article-title":"Urate-induced epigenetic modifications in myeloid cells","volume":"23","author":"Badii","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/cei.13449","article-title":"IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa","volume":"201","author":"Fletcher","year":"2020","journal-title":"Clin. Exp. Immunol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.jaci.2023.05.012","article-title":"Single-cell transcriptomics suggest distinct upstream drivers of IL-17A\/F in hidradenitis versus psoriasis","volume":"152","author":"Kim","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nowowiejska, J., Baran, A., Hermanowicz, J.M., Pryczynicz, A., Sieklucka, B., Pawlak, D., and Flisiak, I. (2023). Gasdermin D (GSDMD) Is Upregulated in Psoriatic Skin-A New Potential Link in the Pathogenesis of Psoriasis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713047"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1111\/j.1462-5822.2006.00751.x","article-title":"Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages","volume":"8","author":"Fink","year":"2006","journal-title":"Cell. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41590-020-0669-6","article-title":"FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation","volume":"21","author":"Hu","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"175091","DOI":"10.1016\/j.ejphar.2022.175091","article-title":"Therapeutic potential of MCC950, a specific inhibitor of NLRP3 inflammasome","volume":"928","author":"Li","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41419-022-04966-8","article-title":"Novel role for caspase 1 inhibitor VX765 in suppressing NLRP3 inflammasome assembly and atherosclerosis via promoting mitophagy and efferocytosis","volume":"13","author":"Jin","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00105-020-04703-2","article-title":"Anakinra therapy in a patient with multifocal pyoderma gangrenosum and hidradenitis suppurativa","volume":"72","author":"Oymanns","year":"2021","journal-title":"Hautarzt"},{"key":"ref_36","first-page":"772","article-title":"Failure of Anakinra in a Case of Severe Hidradenitis Suppurativa","volume":"15","author":"Russo","year":"2016","journal-title":"J. Drugs Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1001\/jamadermatol.2017.2392","article-title":"Canakinumab for Severe Hidradenitis Suppurativa: Preliminary Experience in 2 Cases","volume":"153","author":"Houriet","year":"2017","journal-title":"JAMA Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"615","DOI":"10.4103\/ijdvl.IJDVL_147_16","article-title":"Hidradenitis suppurativa unresponsive to canakinumab treatment: A case report","volume":"83","author":"Tekin","year":"2017","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"855828","DOI":"10.3389\/fphar.2022.855828","article-title":"Gasdermin E: A Prospective Target for Therapy of Diseases","volume":"13","author":"Liao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"116863","DOI":"10.1016\/j.biopha.2024.116863","article-title":"The role of pyroptosis in metabolism and metabolic disease","volume":"176","author":"Zheng","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/s41467-023-36614-w","article-title":"GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis","volume":"14","author":"Wei","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nowowiejska, J., Baran, A., Pryczynicz, A., Hermanowicz, J.M., Sieklucka, B., Pawlak, D., and Flisiak, I. (2023). Gasdermin E (GSDME)\u2014A New Potential Marker of Psoriasis and Its Metabolic Complications: The First Combined Study on Human Serum, Urine and Tissue. Cells, 12.","DOI":"10.3390\/cells12172149"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wei, Y., Wu, Y., Yuan, Z., Wang, J., and Yin, D.L. (2024). GSDME Deficiency Sensitizes Mice to Diet-Induced Obesity by Suppressing Lipolysis. Endocrine Abstracts, Proceedings of the 26th European Congress of Endocrinology, Stockholm, Sweden, 11\u201314 May 2024, Bioscientifica.","DOI":"10.1530\/endoabs.99.OC4.6"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.jaad.2013.11.014","article-title":"The prevalence of metabolic syndrome in patients with hidradenitis suppurativa","volume":"70","author":"Gold","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"\u0141apa, W., Kutaj, A., Kowalczyk, E., G\u0142uszak, P., Welc, N., and Ja\u0142owska, M. (2025). Glucose metabolism disorders in hidradenitis suppurativa: Current evidence and future directions. Forum Dermatologicum, 104845.","DOI":"10.5603\/fd.104845"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/ijd.17186","article-title":"Risk of cardiovascular disorders in hidradenitis suppurativa patients: A large-scale, propensity-matched global retrospective cohort study","volume":"63","author":"Krajewski","year":"2024","journal-title":"Int. J. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"RP101248","DOI":"10.7554\/eLife.101248","article-title":"Gasdermin D-mediated neutrophil pyroptosis drives inflammation in psoriasis","volume":"13","author":"Liu","year":"2024","journal-title":"Elife"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110958","DOI":"10.1016\/j.intimp.2023.110958","article-title":"Inhibition of gasdermin D (GSDMD) as a promising therapeutic approach for atopic dermatitis","volume":"124","author":"Lu","year":"2023","journal-title":"Int. Immunopharmacol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/9\/1258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:44:38Z","timestamp":1760035478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/9\/1258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biology14091258"],"URL":"https:\/\/doi.org\/10.3390\/biology14091258","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]}}}