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Jagged-1是存在于哺乳动物细胞膜上Notch受体的主要配体之一,在许多组织的生长发育中起着重要作用。研究表明Jagged-1-Notch信号参与肿瘤新生血管化,表现为诱导血管特异性酶活化促进内皮细胞分化,导致内皮-间质细胞移行促进血管发育;上调内皮细胞标志分子如血管内皮钙黏附蛋白、血小板内皮细胞黏附分子-1、血管生成素受体-2、纤维连接蛋白、血小板源生长因子受体和α-平滑肌肌动蛋白等的表达,促进内皮和平滑肌细胞分化;与TGF-α和EGF等生长因子激活的通路共同作用促进血管样结构的形成。但也发现Jagged-1-Notch信号通路下游的HERP1通过阻止myocardin而抑制血管平滑肌细胞标志蛋白SM-MHC和平滑肌22-α的表达,同时通过干扰血清应答因子与SM-MHC中含CArG的启动子结合而抑制血管平滑肌细胞的分化;Jagged-1信号通过p21Cip1抑制cyclinD和cdk4的核定位以及Rb蛋白的磷酸化,从而抑制血管内皮细胞的增殖。Jagged-1所呈现的反向双重作用机制仍有待阐明。
Jagged-1 is one of the major ligands for Notch receptors present in mammalian cell membranes and plays an important role in the growth and development of many tissues. Studies have shown that Jagged-1-Notch signaling is involved in neovascularization of the neoplasm, manifested as induction of vascular-specific enzyme activation to promote endothelial cell differentiation, leading to endothelial-stromal cell migration to promote vascular development; upregulation of endothelial cell marker molecules such as vascular endothelial cadherin, Platelet endothelial cell adhesion molecule-1, angiopoietin receptor-2, fibronectin, platelet-derived growth factor receptor and a-smooth muscle actin, and promote the differentiation of endothelial cells and smooth muscle cells; Pathways such as growth factor activation promote the formation of vascular-like structures. However, HERP1 downstream of Jagged-1-Notch signaling pathway was also found to inhibit the expression of vascular smooth muscle cell marker proteins SM-MHC and smooth muscle 22-α by blocking myocardin while interfering with the expression of CArG promoter in SM-MHC Jagged-1 signaling inhibits the proliferation of vascular endothelial cells by inhibiting the nuclear localization of cyclinD and cdk4 and the phosphorylation of Rb protein through p21Cip1. The reverse double-acting mechanism presented by Jagged-1 remains to be elucidated.