Regulation of cell proliferation by HB-EGF in mouse cardiac valve development

HB-EGF 对小鼠心脏瓣膜发育中细胞增殖的调节

• 批准号: 20570183
• 负责人: IWAMOTO Ryo
• 金额: $ 3.08万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20570183/
• 关键词: 細胞・組織; 発生・分化; 増殖因子; 細胞間情報伝達

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.

HB-EGF是EGF生长因子家族的一员，通过抑制间充质细胞增殖在心脏瓣膜发育中发挥重要作用。在这项研究中，我们发现HB-EGF必须与硫酸肝素蛋白聚糖（HSPGs）相互作用才能在这一过程中正常发挥作用。进一步阐明hb - egf介导的细胞增殖抑制的分子机制的研究表明，间充质细胞中EGFR和下游JNK-和p38mapk信号级联参与了生长抑制。此外，当HB-EGF在瓣膜发育中缺失时，egfr信号也参与细胞增殖的上调，这表明HB-EGF/ egfr介导的生长抑制和其他egfr配体/ egfr介导的生长促进的相反信号级联在正常的心脏瓣膜发育中是相互竞争的。

项目成果

Humanized Gene Replacement in Mice Reveals the Contribution of Cancer Stroma-Derived HB-EGF to Tumor Growth.

小鼠中的人源化基因替换揭示了癌症基质衍生的 HB-EGF 对肿瘤生长的贡献。

• 发表时间: 2010
• 期刊: Cell Struct Funct. 35
• 作者: Ichise,T.;Adachi,S.;Ohishi,M.;Ikawa,M.;Okabe,M.;Iwamoto,R.;Mekada,E.
• 通讯作者: Mekada,E.

Physiological functions of diphtheria toxin receptor/HB-EGF.

白喉毒素受体/HB-EGF的生理功能。

• 发表时间: 2010
• 作者: Mekada;E.;Iwamoto;R.;岩本 亮;岩本亮;岩本亮;岩本亮
• 通讯作者: 岩本亮

HB-EGFの生理機能発揮におけるエクトドメイン・シェデイングの役割

胞外域脱落在 HB-EGF 生理功能中的作用

• 发表时间: 2008
• 作者: Mekada;E.;Iwamoto;R.;岩本 亮;岩本亮;岩本亮;岩本亮;岩本亮;岩本亮;岩本亮;岩本亮;岩本亮;岩本亮;岩本 亮
• 通讯作者: 岩本 亮

Anti-human HB-EGF monoclonal antibodies inhibiting ectodomain shedding of HB-EGF and diphtheria toxin binding

• DOI: 10.1093/jb/mvq033
• 发表时间: 2010-07-01
• 期刊: JOURNAL OF BIOCHEMISTRY
• 影响因子: 2.7
• 作者: Hamaoka, Miki;Chinen, Ichino;Mekada, Eisuke
• 通讯作者: Mekada, Eisuke

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

• DOI: 10.1158/0008-5472.can-10-0346
• 发表时间: 2010-07-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Koshikawa, Naohiko;Mizushima, Hiroto;Seiki, Motoharu
• 通讯作者: Seiki, Motoharu