{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:14:46Z","timestamp":1791051286435,"version":"4.1.0"},"reference-count":107,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drug-induced gingival overgrowth (DIGO) is one of the side effects produced by therapeutic agents, most commonly phenytoin, nifedipine and cyclosporin A. However, the precise mechanism of DIGO is not entirely understood. A literature search of the MEDLINE\/PubMed databases was conducted to identify the mechanisms involved in DIGO. The available information suggests that the pathogenesis of DIGO is multifactorial, but common pathogenic sequelae of events emerge, i.e., sodium and calcium channel antagonism or disturbed intracellular handling of calcium, which finally lead to reductions in intracellular folic acid levels. Disturbed cellular functions, mainly in keratinocytes and fibroblasts, result in increased collagen and glycosaminoglycans accumulation in the extracellular matrix. Dysregulation of collagenase activity, as well as integrins and membrane receptors, are key mechanisms of reduced degradation or excessive synthesis of connective tissue components. This manuscript describes the cellular and molecular factors involved in the epithelial\u2013mesenchymal transition and extracellular matrix remodeling triggered by agents producing DIGO.<\/jats:p>","DOI":"10.3390\/ijms24065448","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T05:36:21Z","timestamp":1678685781000},"page":"5448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Drug-Induced Gingival Overgrowth\u2014Molecular Aspects of Drug Actions"],"prefix":"10.3390","volume":"24","author":[{"given":"Agnieszka","family":"Dro\u017adzik","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Dentistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-7168","authenticated-orcid":false,"given":"Marek","family":"Dro\u017adzik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pomeranian Medical University in Szczecin, Powstancow Wlkp 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1001\/jama.1939.02800130028009","article-title":"The treatment of epilepsy with sodium diphenyl hydantoinate","volume":"112","author":"Kimball","year":"1939","journal-title":"J. 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