{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T08:16:17Z","timestamp":1776154577148,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"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":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Studies have shown that <jats:italic>Porphyromonas gingivalis (P. gingivalis)<\/jats:italic>\u00a0can promote the development of chronic kidney disease (CKD). In this study, we explored the epithelial\u2013mesenchymal transition (EMT) process promoted by <jats:italic>P. gingivalis<\/jats:italic> outer membrane vesicles (OMVs) in renal interstitial fibrosis (RIF), thereby providing new ideas for the study of the relationship between periodontitis and CKD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For in vivo experiments, RIF models induced by unilateral ureteral obstruction (UUO) were constructed in 6\u2010week\u2010old C57BL\/6 mice, followed by administration of <jats:italic>P. gingivalis<\/jats:italic> OMVs (100\u00a0\u00b5g) through the tail vein once every other day for 2\u00a0weeks. For in vitro experiments, the RIF model was established by transforming growth factor\u2010beta (TGF\u2010\u03b2)1\u2010induced mouse renal tubular epithelial cells (RTECs), followed by the administration of 100\u00a0\u00b5g <jats:italic>P. gingivalis<\/jats:italic> OMVs. In vivo imaging system (IVIS) imaging and immunofluorescence were used to detect whether peripheral injection of <jats:italic>P. gingivalis<\/jats:italic> OMVs through the tail vein could enter mouse kidney tissue. Serum biochemical assays were performed to detect the renal function of the injected mice. Hematoxylin\u2010eosin (HE) staining and Masson's trichrome staining were used to assess tubulointerstitial lesions and fibrosis. Quantitative reverse transcription\u2010polymerase chain reaction (qRT\u2010PCR) was used to detect gene expression levels of cytokines related to renal inflammation and fibrosis. The expression levels of EMT\u2010related proteins in kidney tissue and RTECs were evaluated by immunofluorescence and Western blotting. The expression levels of EMT\u2010related regulatory factors Snail1 and \u03b2\u2010catenin in the renal tissues of mice in each group were detected by qRT\u2010PCR and Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>P. gingivalis<\/jats:italic> OMVs successfully entered the kidney tissue of the mice via circulation. <jats:italic>P. gingivalis<\/jats:italic> OMVs aggravated renal dysfunction, renal tubulointerstitial lesions, and fibrosis in UUO mice. <jats:italic>P. gingivalis<\/jats:italic> OMVs upregulated the gene expression of inflammatory and fibrosis\u2010related factors. <jats:italic>P. gingivalis<\/jats:italic> OMVs induced renal tubular EMT exacerbation both in vivo and in vitro. <jats:italic>P. gingivalis<\/jats:italic> OMVs upregulated gene and protein expression levels of EMT\u2010related regulatory factors such as \u03b2\u2010catenin and Snail1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>P. gingivalis<\/jats:italic> OMVs can aggravate renal dysfunction, tubulointerstitial disease, and RIF and may further aggravate EMT by regulating the expression of \u03b2\u2010catenin and Snail1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p><jats:italic>Porphyromonas gingivalis<\/jats:italic> is the main pathogenic factor of periodontitis. Chronic kidney disease (CKD) is a global epidemic that affects about 10% of the world's population. Renal interstitial fibrosis (RIF) is the common pathway of progression from CKD to end\u2010stage kidney disease (ESKD). During the development of RIF, renal tubular epithelial cells (RTECs), as the most vulnerable intrinsic cells of the kidney, can be transformed into myofibroblasts through epithelial\u2013mesenchymal transition (EMT). <jats:italic>P. gingivalis<\/jats:italic> outer membrane vesicles (OMVs) can reach deep tissues and activate host inflammatory response. Several studies have shown that <jats:italic>P. gingivalis<\/jats:italic> can increase kidney inflammation and immunosuppression through complex mechanisms, induce renal insufficiency, and affect CKD development. However, there are few reports about <jats:italic>P. gingivalis<\/jats:italic> OMVs and EMT. Our study found that <jats:italic>P. gingivalis<\/jats:italic> OMVs can aggravate renal dysfunction, tubulointerstitial disease, and RIF and may further aggravate EMT by regulating the expression of \u03b2\u2010catenin and Snail1. Therefore, this finding provides a new strategy for preventing CKD\/EMT from the perspective of treating periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.24-0506","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T08:17:09Z","timestamp":1745914629000},"page":"920-932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of <i>Porphyromonas gingivalis<\/i> outer membrane vesicles on renal tubule epithelial\u2013mesenchymal transition"],"prefix":"10.1002","volume":"96","author":[{"given":"Zhaorong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Periodontology School of Stomatology China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoucheng","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muzhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9990-6261","authenticated-orcid":false,"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology China Medical University  Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.230"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"1","article-title":"Kidney Disease: improving Global Outcomes (KDIGO) CKD Work Group. 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