{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T03:04:41Z","timestamp":1779937481680,"version":"3.53.1"},"reference-count":47,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centre of Postgraduate Medical Education","award":["501-1-019-56-23"],"award-info":[{"award-number":["501-1-019-56-23"]}]},{"name":"Centre of Postgraduate Medical Education","award":["UMO-2017\/25\/B\/NZ5\/02949"],"award-info":[{"award-number":["UMO-2017\/25\/B\/NZ5\/02949"]}]},{"name":"National Science Centre, Poland","award":["501-1-019-56-23"],"award-info":[{"award-number":["501-1-019-56-23"]}]},{"name":"National Science Centre, Poland","award":["UMO-2017\/25\/B\/NZ5\/02949"],"award-info":[{"award-number":["UMO-2017\/25\/B\/NZ5\/02949"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Cholesteatoma is a specific medical condition involving the abnormal, non-cancerous growth of skin-like tissue in the middle ear, potentially leading to a collection of debris and even infections. The receptor for advanced glycation (RAGE) and its ligand, high-mobility box 1 (HMGB1), are both known to be overexpressed in cholesteatoma and play a potential role in the pathogenesis of the disease. In this study, we investigated the role of small extracellular vesicles (sEVs) in carrying HMGB1 and inducing disease-promoting effects in cholesteatoma. No significant differences in the concentration of isolated sEVs in the plasma of cholesteatoma patients (n = 17) and controls (n = 22) were found (p &gt; 0.05); however, cholesteatoma-derived sEVs carried significantly higher levels of HMGB1 (p &lt; 0.05). In comparison to sEVs isolated from the plasma of controls, cholesteatoma-derived sEVs significantly enhanced keratinocyte proliferation and IL-6 production (p &lt; 0.05), potentially by engaging multiple activation pathways including MAPKp44\/p42, STAT3, and the NF-\u03baB pathway. Thus, HMGB1(+) sEVs emerge as a novel factor potentially promoting cholesteatoma progression.<\/jats:p>","DOI":"10.3390\/diagnostics13223469","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T09:23:43Z","timestamp":1700213023000},"page":"3469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["HMGB1 Carried by Small Extracellular Vesicles Potentially Plays a Role in Promoting Acquired Middle Ear Cholesteatoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Micha\u0142 W.","family":"\u0141uczak","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02906, USA"},{"name":"Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4211-7664","authenticated-orcid":false,"given":"Karolina","family":"D\u017caman","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5211-0824","authenticated-orcid":false,"given":"\u0141ukasz","family":"Zar\u0119ba","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-8377","authenticated-orcid":false,"given":"Katarzyna","family":"Czerwaty","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Siewiera","sequence":"additional","affiliation":[{"name":"Department of Hyperbaric Medicine, Military Institute of Medicine-National Research Institute, 00-902 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5657-0163","authenticated-orcid":false,"given":"Alicja","family":"G\u0142uszko","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9993-9266","authenticated-orcid":false,"given":"Ewa","family":"Olszewska","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Brzost","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The Children\u2019s Memorial Health Institute, 00-328 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ireneusz","family":"Kantor","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5206-137X","authenticated-orcid":false,"given":"Miros\u0142aw J.","family":"Szczepa\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland"},{"name":"Department of Otolaryngology, Centre of Postgraduate Medical Education, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5561-2184","authenticated-orcid":false,"given":"Nils","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Molecular biology of cholesteatoma","volume":"55","author":"Maniu","year":"2014","journal-title":"Rom. 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