2007 Fiscal Year Final Research Report Summary
Possible important role of DNA methylation in the induction of SLE ; relating to the new therapeutic strategy of SLE
| Project/Area Number |
17591057
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Juntendo University |
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Principal Investigator |
SEKIGAWA Iwao Juntendo University, School of Medicine, professor (80179332)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Systemic lupus ervthematosus / Human endogenous retovirus / Epigenetics / DNA methylation / DNMT- 1 / DNA microarrav / Estrogen |
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| Research Abstract |
The precise pathogenesis of systemic lupus erythematosus (SLE) is still unclear, however, autoantibodies are thought to be produced by increased transcription of certain elf antigens, such as human endogenous retroviruses (HERV). We have found that transcription of HERV is increased in patients with SLE as compared to normal individuals and this increase is related to quantitative decreasing of DNA methyl transferase (DNMT)-1. In addition, theses increasing effects of transcription of endogenous self antigens seem to be related to sex hormone such as estrogen. In order to investigate the effect of sex hormones on the gene expressions, changes in gene expression in peripheral blood mononuclear cells (PBMC) were examined during the menstrual cycle in females, under the comparison of gene expression of patients with SLE using DNA microarray methods. Based on these findings, certain genes (such as the tumor necrosis factor receptor superfamily, member 14; TNFRSF14, and signal regulatory protein, gamma; SIRPG) appear to contribute to gender difference of SLE. These findings may open the way to a new therapeutic strategy of SLE.
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