{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:35:39Z","timestamp":1792852539074,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Iraqi Ministry of Higher Education and Scientific Research"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Epithelial\u2010mesenchymal transition (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>) is a process by which epithelial cells acquire a mesenchymal\u2010like phenotype and this may be induced by exposure to gram\u2010negative bacteria. It has been proposed that <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> is responsible for compromising epithelial barrier function in the pathogenesis of several diseases. However, the possible role of <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> in the pathogenesis of periodontitis has not previously been investigated. The aim of this study therefore was to investigate whether gram\u2010negative, anaerobic periodontal pathogens could trigger <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> in primary oral keratinocytes in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Primary oral keratinocytes were harvested from labial mandibular mucosa of Wistar Han rats. Cells were exposed to heat\u2010killed <jats:italic>Fusobacterium nucleatum<\/jats:italic> and <jats:italic>Porphyromonas gingivalis<\/jats:italic> (100 bacteria\/epithelial cell) and to 20\u00a0\u03bcg\/mL of <jats:italic>Escherichia coli<\/jats:italic> lipopolysaccharide over an 8\u2010day period. Exposure to bacteria did not significantly change epithelial cell number or vitality in comparison with unstimulated controls at the majority of time\u2010points examined. Expression of <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> marker genes was determined by semiquantitative <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> at 1, 5, and 8\u00a0days following stimulation. The expression of <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> markers was also assessed by immunofluorescence (E\u2010cadherin and vimentin) and using immunocytochemistry to determine Snail activation. The loss of epithelial monolayer coherence, in response to bacterial challenge, was determined by measuring trans\u2010epithelial electrical resistance. The induction of a migratory phenotype was investigated using scratch\u2010wound and transwell migration assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exposure of primary epithelial cell cultures to periodontal pathogens was associated with a significant decrease in transcription (~3\u2010fold) of E\u2010cadherin and the upregulation of N\u2010cadherin, vimentin, Snail, matrix metalloproteinase\u20102 (~3\u20105 fold) and toll\u2010like receptor 4. Bacterial stimulation (for 8 days) also resulted in an increased percentage of vimentin\u2010positive cells (an increase of 20% after stimulation with <jats:italic>P.\u00a0gingivalis<\/jats:italic> and an increase of 30% after stimulation with <jats:italic>F.\u00a0nucleatum<\/jats:italic>, compared with controls). Furthermore, periodontal pathogens significantly increased the activation of Snail (60%) and cultures exhibited a decrease in electrical impedance (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) in comparison with unexposed controls. The migratory ability of the cells increased significantly in response to bacterial stimulation, as shown by both the number of migrated cells and scratch\u2010wound closure rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Prolonged exposure of primary rat oral keratinocyte cultures to periodontal pathogens generated <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>\u2010like features, which introduces the possibility that this process may be involved in loss of epithelial integrity during periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12546","type":"journal-article","created":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T05:04:39Z","timestamp":1524891879000},"page":"565-574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Potential role of periodontal pathogens in compromising epithelial barrier function by inducing epithelial\u2010mesenchymal transition"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-6715","authenticated-orcid":false,"given":"A. A.","family":"Abdulkareem","sequence":"first","affiliation":[{"name":"Department of Periodontics College of Dentistry University of Baghdad  Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. M.","family":"Shelton","sequence":"additional","affiliation":[{"name":"Biomaterials School of Dentistry Institute of Clinical Sciences College of Medical and Dental Sciences The University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Landini","sequence":"additional","affiliation":[{"name":"Oral Pathology School of Dentistry Institute of Clinical Sciences College of Medical and Dental Sciences The University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Oral Biology &amp; Periodontology School of Dentistry Institute of Clinical Sciences College of Medical and Dental Sciences The University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9089-687X","authenticated-orcid":false,"given":"M. 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