1998 Fiscal Year Final Research Report Summary
Development of preventive for periodontitis by using avtivin that indices apoptosis and suppresses the production of IL-1
| Project/Area Number |
09557155
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Conservative dentistry
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
NISHIHARA Tatsuji National Institute of Infectious Diseases, Department of Oral Science, Chief of Laboratory of Periodontology, 口腔科学部, 室長 (80192251)
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| Co-Investigator(Kenkyū-buntansha) |
ETO Yuzuru Ajinomoto Company, Inc., Central Research Laboratories, Senior Researcher, 中央研究所, 主席研究官
OKAHASHI Nobuo National Institute of Infectious Diseases, Department of Oral Science, Senior Re, 口腔科学部, 主任研究官 (40150180)
SUGINO Hiromu The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (50211305)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Activin / apotosis / interleukin-1 / interleukin-1 receptor antagonist / cell-cycle arrest / periodontitis |
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| Research Abstract |
Activins transduce their signals through binding to activin type I receptor (ActR-I) and activin type II receptor (ActR-II), both containing a serine/threonine kinase domain. In this study, we have clarified the role of activin type I receptors in activin A signaling for growth inhibition in HS-72 mouse B cell hybridoma cells. Overexpression of ActR-I suppressed activin A-induced cell cycle arrest in the G1 phase caused by inhibiting Rb phosphorylation through inducting p21^<CIP1/WAF1> and subsequent apoptosis. In contrast, HS-72 cells that overexpressed ActR-IB facilitated activin A-induced apoptosis. These findings suggest that the ActR-I/ActR-IB expression ratio could regulate cell cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.Recently, Activins were found to relay signals from serine/threonine kinase receptors in membrane to nucleus via intracellular Sma-and Mad-related (Smad) proteins. Inhibitory Smad proteins are known to prevent the interaction between the serine/threonine kinase receptors and pathway-restricted Smad proteins. Smad7 was identified as a TGF-beta-inducible antagonist of TGF-beta signaling. In this study, we found that the mRNA expression of Smad7 was induced by activin A in HS-72 cells. The ectopic expression of mouse Smad7 in HS-72 cells suppressed the activin A-induced cell-cycle arrest in the G1 phase by abolishing the activin A-induced expression of p21^<CIP1/WAF1> and hypophosphorylation of retinoblastoma protein.
Furthermore, Smad7 expression suppressed activin A-induced apoptosis in HS-72 cells. Thus, our data indicate that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis of B lineage cells.
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