{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:28:35Z","timestamp":1780439315871,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T00:00:00Z","timestamp":1543449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Human periodontal ligament fibroblasts (HPDLFs) represent the first line of defense against pathogens in the periodontal tissue. <jats:italic>Porphyromonas gingivialis<\/jats:italic> (<jats:italic>P.\u00a0gingivalis<\/jats:italic>) has been known to be most strongly associated with periodontitis. MicroRNA (miR)\u2010146a is involved in the inflammatory regulation of periodontitis. However, the regulatory mechanism of miR\u2010146a on in <jats:italic>P.\u00a0gingivalis<\/jats:italic>\u2010induced inflammation response in HPDLFs was still unclear. The aim of this study was to investigate whether miR\u2010146a plays a key role in <jats:italic>P. gingvalis<\/jats:italic>\u2010induced inflammation responses through regulation of TRAF6 in HPDLFs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MiR\u2010146a expression was measured by real\u2010time polymerase chain reaction (PCR) in HPDLFs stimulated with <jats:italic>P.\u00a0gingivalis<\/jats:italic> and its lipopolysaccharide (LPS). IL\u20101\u00df, IL\u20106, and IL\u20108 were determined by enzyme\u2010linked immunosorbent assay (ELISA) in the culture supernatants of HPDLFs after transfected with miR\u2010146a mimic or inhibitor. Meanwhile, the expression of TRAF6 was measured by real\u2010time PCR and Western blot. Then, we used luciferase reporter assay to detect whether miR\u2010146a binds to the 3\u2032\u2010UTR of TRAF6. By using small interfering RNA (siRNA) of TRAF6, the phosphorylation of p38 mitogen\u2010activated protein kinase (MAPK) was measured by Western blot. Finally, after inhibition of TRAF6 and p38 in HPDLFs, we analyzed the expression of miR\u2010146a upon <jats:italic>P.\u00a0gingivalis<\/jats:italic> challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>P.\u00a0gingivalis<\/jats:italic> and its LPS significantly induced miR\u2010146a expression in HPDLFs. Overexpression of miR\u2010146a significantly suppressed the IL\u20101\u00df, IL\u20106 and IL\u20108 secretion, TRAF6 expression, and p38 phosphorylation. In contrast, the levels of these indexes significantly increased by inhibition of miR\u2010146a. Furthermore, MiR\u2010146a directly binds to the 3\u2032\u2010UTR of TRAF6 in <jats:italic>P.\u00a0gingivalis<\/jats:italic>\u2010induced HPDLFs, but not in <jats:italic>P.\u00a0gingivalis<\/jats:italic> LPS stimulation. Suppression of TRAF6 could inhibit the phosphorylation of p38. Finally, inhibition of TRAF6 and p38 significantly abolished <jats:italic>P.\u00a0gingivalis<\/jats:italic>\u2010induced miR\u2010146a upregulation in HPDLFs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MiR\u2010146a contribute to negative regulation of <jats:italic>P.\u00a0gingivalis<\/jats:italic>\u2010induced proinflammatory cytokines secretion in HPDLFs though TRAF6\/p38 MAPK pathway. Maintaining miR\u2010146a homeostasis plays a key role in controlling inflammatory response in periodontal tissues.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.18-0190","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T05:45:12Z","timestamp":1540964712000},"page":"391-399","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["MicroRNA\u2010146a negatively regulates the inflammatory response to <i>Porphyromonas gingivalis<\/i> in human periodontal ligament fibroblasts via TRAF6\/p38 pathway"],"prefix":"10.1002","volume":"90","author":[{"given":"Lu","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Stomatology Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Li","sequence":"additional","affiliation":[{"name":"The affiliated Stomatology Hospital of Kunming medical 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