Secreted caveolin-1 enhances periodontal inflammation by targeting gingival fibroblasts
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- Takizawa Naoki
- Division of Periodontics, Department of Conservative Dentistry and Oral Rehabilitation, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan
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- Sawada Shunsuke
- Division of Periodontics, Department of Conservative Dentistry and Oral Rehabilitation, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan
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- Chosa Naoyuki
- Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate, Japan
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- Ishisaki Akira
- Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate, Japan
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- Naruishi Koji
- Division of Endodontics, Department of Conservative Dentistry and Oral Rehabilitation, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan
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Abstract
Caveolin-1 (Cav-1) is a membrane protein. Recently, it has been reported that secreted Cav-1 induces angiogenesis in inflammatory microenvironment. However, it is unclear that Cav-1 regulates gingival inflammation. Therefore, we investigated the Cav-1 function to periodontal cells. Expression of Cav-1 in human periodontitis tissues was examined pathologically. Secretion of Cav-1 from human gingival fibroblasts (HGFs) or human periodontal ligament cells (HPLFs) treated with IL-1β and TNF-α was examined using Western blotting. Likewise, intracellular signals induced by Cav-1 were examined. Finally, we examined whether the secreted Cav-1 induces production of inflammatory mediators in HGFs using ELISA or qRT-PCR. Pathologically, high expression of Cav-1 was observed in human periodontitis tissues. Cav-1 secretion increased in both cultured HGFs and HPLFs treated with IL-1β and TNF-α. Cav-1 induced phosphorylation of JNK and ERK, but not Stat3 in HGFs. Furthermore, Cav-1 increased proMMP-1 and VEGF secretion in HGFs, and the VEGF secretion was statistically suppressed by JNK inhibitor SP600125, but not ERK inhibitor PD98059. ProMMP-1 secretion was suppressed statistically by both SP600125 and PD98059. In addition, Cav-1 increased significantly MMP-1, -10 and -14 mRNA expressions, whereas no increase of TIMPs mRNA was observed in HGFs treated with Cav-1. These data suggest that secreted Cav-1 derived from periodontal fibroblastic cells enhances inflammation-related several proteases and VEGF secretion in HGFs via MAPKs pathway, resulting in progression of periodontitis through induction of tissue degradation or angiogenesis.
Journal
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- Biomedical Research
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Biomedical Research 34 (1), 1-11, 2013
Biomedical Research Press