{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:00:52Z","timestamp":1772020852439,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Riga Stradi\u0146\u0161 University","award":["6-DN-20\/1\/2022"],"award-info":[{"award-number":["6-DN-20\/1\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives. The aim of this study was to compare the distribution of proliferation markers (Ki-67, NF-\u03ba\u03b2), tissue-remodeling factors (MMP-2, MMP-9, TIMP-2, TIMP-4), vascular endothelial growth factor (VEGF), interleukins (IL-1 and IL-10), human beta defensins (H\u03b2D-2 and H\u03b2D-4) and Sonic hedgehog gene protein in cholesteatoma and control skin. Methods. Nineteen patient cholesteatoma tissues and seven control skin materials from cadavers were included in the study and stained immunohistochemically. Results. Statistically discernible differences were found between the following: the Ki-67 in the matrix and the Ki-67 in the skin epithelium (p = 0.000); the Ki-67 in the perimatrix and the Ki-67 in the connective tissue (p = 0.010); the NF-\u03ba\u03b2 in the cholesteatoma matrix and the NF-\u03ba\u03b2 in the epithelium (p = 0.001); the MMP-9 in the matrix and the MMP-9 in the epithelium (p = 0.008); the H\u03b2D-2 in the perimatrix and the H\u03b2D-2 in the connective tissue (p = 0.004); and the Shh in the cholesteatoma\u2019s perimatrix and the Shh in the skin\u2019s connective tissue (p = 0.000). Conclusion. The elevation of Ki-67 and NF-\u03ba\u03b2 suggests the induction of cellular proliferation in the cholesteatoma. Intercorrelations between VEGF, NF-\u03ba\u03b2 and TIMP-2 induce neo-angiogenesis in adult cholesteatoma. The similarity in the expression of IL-1 and IL-10 suggests the dysregulation of the local immune status in cholesteatoma. The overexpression of the Sonic hedgehog gene protein in the cholesteatoma proves the selective local stimulation of perimatrix development.<\/jats:p>","DOI":"10.3390\/medicina59020306","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:01:45Z","timestamp":1675825305000},"page":"306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Morphopathogenesis of Adult Acquired Cholesteatoma"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-6512","authenticated-orcid":false,"given":"Kristaps","family":"Dambergs","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Riga Stradi\u0146\u0161 University, Pilsonu Street 13, LV-1002 Riga, Latvia"},{"name":"Children\u2019s Clinical University Hospital, Vienibas Gatve 45, LV-1004 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunta","family":"Sumeraga","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Riga Stradi\u0146\u0161 University, Pilsonu Street 13, LV-1002 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-4666","authenticated-orcid":false,"given":"M\u0101ra","family":"Pilmane","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Anatomy and Anthropology, Riga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"854024","DOI":"10.1155\/2015\/854024","article-title":"Updates and knowledge gaps in cholesteatoma research","volume":"2015","author":"Kuo","year":"2015","journal-title":"Biomed. 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