Regulation of cell proliferation by HB-EGF in mouse 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。

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.