2004 Fiscal Year Final Research Report Summary
Antiatherogenic action of estrogen through inhibition of pathological proliferation in vascular smooth muscle sells
| Project/Area Number |
14370523
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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 | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Yamagata University |
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Principal Investigator |
KURACHI Hirohisa Yamagata University, Faculty of Medicine, Professor and chairman, 医学部, 教授 (40153366)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHARA Kenji Yamagata University, Faculty of Medicine, Associate Professor, 医学部, 講師 (80250934)
TAKAHASHI Kazuhiro Yamagata University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (20292427)
ABE Akiko Yamagata University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (30359567)
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| Project Period (FY) |
2002 – 2004
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| Keywords | estrogen receptor / atherosclerosis / apoptosis / phosphorylation / MAP kinase pathway / cyclin D1 / selective estrogen receptor modulator / mammary carcinoma |
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| Research Abstract |
According to the scheduled research program, we obtained the results using human and the primary culture of rat vascular smooth muscle cells (SMC). (1)SMC expresses both estrogen receptor (ER) α and β. (2)SMC proliferates in the presence of high concentrations of serum and platelet-derived growth factor, and estrogen (E2) inhibited the proliferation. (3)Three kinds of MAP kinase family of ERK, JNK and p38 pathways, were investigated for the non-genomic action by E2: E2 strongly suppressed the ERK pathway but it did not affect the JNK. E2 also induced the phosphorylation of p38 MAP kinase which induced apoptosis in SMC. (4)The apoptosis was involved in the inhibition of SMC proliferation by E2. Next, we investigated the genomic mechanism. (1)E2 reduced the proliferation of SMC by inhibiting the progression of cell cycle into S phase. (2)E2 suppressed the amount of cyclin D 1 protein and Rb phosphorylation. (3)ERα was required for the E2-induced inhibition of SMC proliferation. Furthermore, we studied the role of raloxifene, a selective estrogen receptor modulator, in the proliferation of SMC and mammary carcinoma cells. We found that raloxifene like estrogen, inhibited the SMC proliferation by reducing the cyclin D1 level and Rb phosphorylation (agonistic to estrogen), whereas it inhibited the estrogen-induced cell proliferation in mammary carcinoma cells (antagonistic).
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