FGF-1-dependent proliferative and migratory responses are impaired in senescent human umbilical vein endothelial cells and correlate with the inability to signal tyrosine phosphorylation of fibroblast growth factor receptor-1 substrates.
FGF-1-dependent proliferative and migratory responses are impaired in senescent human umbilical vein endothelial cells and correlate with the inability to signal tyrosine phosphorylation of fibroblast growth factor receptor-1 substrates.
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DOI：
10.1083/jcb.134.3.783
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发表时间：
1996-08
期刊：
影响因子：
--
通讯作者：
Maciag T
中科院分区：
文献类型：
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作者：
Garfinkel S;Hu X;Prudovsky IA;McMahon GA;Kapnik EM;McDowell SD;Maciag T
衰老细胞不增殖响应外源性生长因子，但细胞表面上的生长因子受体的数量和亲和力似乎是类似的衰老细胞群体。为了确定受体信号传导是否存在缺陷，我们分析了人脐静脉内皮细胞（HUVEC），因为HUVEC的生长完全依赖于FGF的存在。我们报告说，在衰老和衰老的HUVEC群体，FGF-1诱导细胞周期特异性基因的表达，这表明功能性FGF受体（FGFR）可能存在于这些细胞的表面上。然而，FGFR-1底物Src和coronin的酪氨酸磷酸化在衰老的HUVEC中受损，并且仅衰老细胞群体表现出FGF-1依赖性Src酪氨酸激酶活性。此外，我们证明，衰老的HUVEC不能迁移响应FGF-1，这些数据与改变组织的粘着斑网站。这些数据表明，基因表达的诱导不足以促进衰老HUVEC中的增殖或迁移表型，并且FGFR-1信号转导途径的减弱可能与衰老HUVEC不能增殖和/或迁移有关。
Senescent cells do not proliferate in response to exogenous growth factors, yet the number and affinity of growth factor receptors on the cell surface appear to be similar to presenescent cell populations. To determine whether a defect in receptor signaling exists, we analyzed human umbilical vein endothelial cells (HUVEC) since HUVEC growth is absolutely dependent upon the presence of FGF. We report that in both presenescent and senescent HUVEC populations, FGF-1 induces the expression of cell cycle-specific genes, suggesting that functional FGF receptor (FGFR) may exist on the surface of these cells. However, the tyrosine phosphorylation of FGFR-1 substrates, Src and cortactin, is impaired in senescent HUVEC, and only the presenescent cell populations exhibit a FGF-1-dependent Src tyrosine kinase activity. Moreover, we demonstrate that senescent HUVEC are unable to migrate in response to FGF-1, and these data correlate with an altered organization of focal adhesion sites. These data suggest that the induction of gene expression is insufficient to promote a proliferative or migratory phenotype in senescent HUVEC and that the attenuation of the FGFR-1 signal transduction pathway may be involved in the inability of senescent HUVEC to proliferate and/or migrate.