2010 Fiscal Year Final Research Report
Regulation of cell proliferation by HB-EGF in mouse cardiac valve development
| Project/Area Number |
20570183
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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 |
Cell biology
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| Research Institution | Osaka University |
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Principal Investigator |
IWAMOTO Ryo Osaka University, 微生物病研究所, 准教授 (10213323)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 細胞・組織 / 発生・分化 / 増殖因子 / 細胞間情報伝達 |
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| Research Abstract |
HB-EGF, a member of the EGF family of growth factors, plays an important role in cardiac valve development by suppressing mesenchymal cell proliferation. In this study, we reveal that HB-EGF must interact with heparan sulfate proteoglycans (HSPGs) to properly function in this process. Further study to elucidate the molecular mechanism involved in HB-EGF-mediated suppression of cell proliferation suggests that EGFR and the downstream JNK- and p38MAPK-signaling cascades in mesenchymal cells are involved in the growth inhibition. Moreover, EGFR-signaling is also involved in the up-regulation of cell proliferation when HB-EGF is deleted in developing valves, suggesting that the opposite signaling cascades of HB-EGF/EGFR-mediated growth-inhibition and the other EGFR-ligand(s)/EGFR-mediated growth promotion are competing in normal cardiac valve development.
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Research Products
(14 results)
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[Journal Article] Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into a heparin-independent growth factor.2010
Author(s)
Koshikawa, N., Mizushima, H., Minegishi, T., Iwamoto R., Mekada, E., Seiki, M.
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Journal Title
Cancer Res. 70
Pages: 6093-6103
Peer Reviewed
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[Journal Article] HB-EGF function in cardiac valve development requires interaction with heparan sulfate proteoglycans.2010
Author(s)
Iwamoto R.^*, Mine, N., Kawaguchi, T., Minami, S., Saeki, K., Mekada, E.(^*corresponding author)
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Journal Title
Development 137
Pages: 2205-2214
Peer Reviewed
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[Journal Article] Anti-human HB-EGF monoclonal antibodies inhibiting ectodomain shedding of HB-EGF and diphtheria toxin binding.2010
Author(s)
Hamaoka, M., Chinen, I., Murata, T., Takashima, S., Iwamoto R., Mekada, E.
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Journal Title
J.Biochem. 148
Pages: 55-69
Peer Reviewed
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[Journal Article] Humanized gene replacement in mice reveals the contribution of cancer stroma-derived HB-EGF to tumor growth.2010
Author(s)
Ichise, T., Adachi, S., Ohishi, M., Ikawa, M., Okabe, M., Iwamoto R., Mekada, E.
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Journal Title
Cell Struct. Funct. 35
Pages: 3-13
Peer Reviewed
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[Journal Article] HB-EGF2008
Author(s)
Mekada, E., Iwamoto R.
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Journal Title
UCSD-Nature Molecule Pages.(doi:10.1038/mp.a002932.01)
Peer Reviewed
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