| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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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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