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Rat models of periodontitis and periodontitis combined with hypertension were established, with healthy rats serving as the control group. Periodontal tissues from each group were collected for transcriptomic and metabolomic sequencing. Subsequently, differential genes and metabolites were analyzed in the periodontitis with hypertension group compared to the control group, as well as in the periodontitis with hypertension group compared to the periodontitis group. Gene Ontology and KEGG enrichment analyses were performed, and a joint analysis of differential genes and metabolites was conducted. A total of 631 differential mRNAs and 67 differential metabolites were identified in the periodontitis with hypertension group compared to the control group. The differential genes and metabolites were mainly enriched in the pathways of phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, and arginine and proline metabolism. In the periodontitis with hypertension group compared to the periodontitis group, 135 differential mRNAs and 24 differential metabolites were identified. The differential genes and metabolites were primarily enriched in the pathways of arginine biosynthesis, cysteine and methionine metabolism, and biosynthesis of amino acids. Citrulline significantly suppresses the production of reactive oxygen species and the expression of the inflammatory cytokine interleukin-8 (IL-8) in gingival fibroblasts. Hypertension may promote the development of periodontitis by altering interferon-inducible genes and the arginine metabolism-related pathway. Citrulline represents a potential therapeutic option for periodontitis.<\/jats:p>","DOI":"10.1038\/s41598-026-48279-8","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:38:15Z","timestamp":1776062295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated transcriptomic and metabolomic analysis to elucidate key genes and signaling pathways involved in the promotion of periodontitis by hypertension"],"prefix":"10.1038","volume":"16","author":[{"given":"Haiqing","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenrui","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulian","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lufei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"48279_CR1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1600-0757.2012.00457.x","volume":"62","author":"RJ Genco","year":"2013","unstructured":"Genco, R. 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