title: Involvement of protease-activated receptor 4 in over-expression of matrix metalloproteinase 9 induced by Porphyromonas gingivalis.
abstract: Porphyromonas gingivalis, a periodontal pathogen, is epidemiologically associated with oral squamous cell carcinoma (OSCC). Matrix metalloproteinase 9 (MMP9) which degrades the extracellular matrix and basement membrane components has been implicated in invasion and metastasis of tumor cells. We previously reported that P. gingivalis promoted cellular invasion of carcinoma SAS cells, an established cell line from patients with squamous cell carcinoma of the tongue, by induction of MMP9 production via proteinase-activated receptor 2. In this study, we further examined alternative signaling pathways mediating inactive precursor of MMP9 (proMMP9) production induced by P. gingivalis in SAS cells. Following P. gingivalis infection, PAR4 mRNA expression was increased and proMMP9 production was enhanced, leading to acceleration of SAS cell invasion. Small interfering RNA knockdown of PAR4 gene abrogated both proMMP9 expression and cellular invasion induced by P. gingivalis in SAS cells. Moreover, the phosphorylation of p38 and ERK1/2 was reduced in PAR4 gene knockdown cells infected with P. gingivalis, whereas nuclear translocation of NF-kB was not inhibited. These results suggest that P. gingivalis activates PAR4 signaling pathways, leading proMMP9 over-expression and cellular invasion in OSCC cells.
authors: Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu, 501-0296, Japan, hinaba@dent.asahi-u.ac.jp.
authors: Hiroaki
authors: H
authors: Inaba
authors: Atsuo
authors: A
authors: Amano
authors: Richard J
authors: RJ
authors: Lamont
authors: Yukitaka
authors: Y
authors: Murakami
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D018179:Receptors, Thrombin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018179:Receptors, Thrombin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; C112908:protease-activated receptor 4