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Human gingival fibroblasts (HGFs) as the main resident cells of human gingiva play a key role in regulating matrix metalloproteinases (MMPs) and contribute to periodontal homeostasis. This study investigated the expression and regulation of MMPs1-3 and tissue inhibitors of MMP-1 (TIMP-1) in HGFs in response to<jats:italic>P. gingivalis<\/jats:italic>LPS<jats:sub>1435\/1449<\/jats:sub>and LPS<jats:sub>1690<\/jats:sub>and hexa-acylated<jats:italic>E. coli<\/jats:italic>LPS as a reference. The expression of MMPs 1\u20133 and TIMP-1 was evaluated by real-time PCR and ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The MMP-3 mRNA and protein were highly upregulated in<jats:italic>P. gingivalis<\/jats:italic>LPS<jats:sub>1690<\/jats:sub>- and<jats:italic>E. coli<\/jats:italic>LPS-treated cells, whereas no induction was observed in<jats:italic>P. gingivalis<\/jats:italic>LPS<jats:sub>1435\/1449<\/jats:sub>-treated cells. On the contrary, the expression of MMP-1 and \u22122 was not significantly affected by<jats:italic>P. gingivalis<\/jats:italic>LPS lipid A heterogeneity. The TIMP-1 mRNA was upregulated in<jats:italic>P. gingivalis<\/jats:italic>LPS<jats:sub>1435\/1449<\/jats:sub>- and<jats:italic>E. coli<\/jats:italic>LPS-treated cells. Next, signal transduction pathways involved in<jats:italic>P. gingivalis<\/jats:italic>LPS-induced expression of MMP-3 were examined by blocking assays. Blockage of p38 MAPK and ERK significantly inhibited<jats:italic>P. gingivalis<\/jats:italic>LPS<jats:sub>1690<\/jats:sub>-induced MMP-3 expression in HGFs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present findings suggest that the heterogeneous lipid A structures of<jats:italic>P. gingivalis<\/jats:italic>LPS differentially modulate the expression of MMP-3 in HGFs, which may play a role in periodontal pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2180-13-73","type":"journal-article","created":{"date-parts":[[2013,3,30]],"date-time":"2013-03-30T09:13:55Z","timestamp":1364634835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The expression and regulation of matrix metalloproteinase-3 is critically modulated by Porphyromonas gingivalis lipopolysaccharide with heterogeneous lipid A structures in human gingival fibroblasts"],"prefix":"10.1186","volume":"13","author":[{"given":"Thanuja D K","family":"Herath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaminda J","family":"Seneviratne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P","family":"Darveau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cun-Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijian","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,3,30]]},"reference":[{"key":"1936_CR1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1177\/0022034511402080","volume":"23","author":"LJ Jin","year":"2011","unstructured":"Jin LJ, Armitage GC, Klinge B, Lang NP, Tonetti M, Williams RC: Global oral health inequalities: task group\u2013periodontal disease. 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