| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
HB-EGF plays an indispensable role in suppression of cell proliferation during mouse valvulogenesis. HB-EGF binds to and activates ErbB1 and ErbB4. We investigated the role of ErbB receptors in valvulogenesis in vivo using ErbB1- and ErbB4-deficient mice, and an ex vivo model of endocardial cushion explants. HB-EGF suppresses valve mesenchymal cell proliferation through a heterodimer of ErbB1 and ErbB4, and certain ErbB1-ligand(s) promotes the proliferation through a homodimer of ErbB1. A rescue experiment with the cleavable (JM-a) or uncleavable (JM-b) isoform of ErbB4 in ERBB4 null cells suggests that intracellular domain of ErbB4 rather than the membrane-anchored tyrosine kinase achieves the suppression. Moreover, cytoplasmic region that is contained in both CYT-1 and CYT-2 subtypes of ErbB4 is essential for the suppression. These results predict that HB-EGF-ErbB4 signaling axis may be applicable for cancer therapy of the next generation.
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