Cell Density-Dependent Fibroblast Growth Factor-2 Signaling Regulates Syndecan-4 Expression in Cultured Vascular Endothelial Cells
Cell Density-Dependent Fibroblast Growth Factor-2 Signaling Regulates Syndecan-4 Expression in Cultured Vascular Endothelial Cells
复制标题
细胞密度依赖性成纤维细胞生长因子-2信号转导调控血管内皮细胞Syndecan-4的表达
DOI：
10.3390/ijms21103698
复制
发表时间：
2020-05-01
影响因子：
5.6
通讯作者：
Kaji, Toshiyuki
中科院分区：
文献类型：
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作者：
Hara, Takato;Yabushita, Shiori;Kaji, Toshiyuki
Syndecan-4是跨膜硫酸乙酰肝素蛋白聚糖的syndecan家族的成员，并且参与血管内皮细胞中的细胞保护、增殖和血液凝固-纤维蛋白溶解系统。硫酸乙酰肝素链使成纤维细胞生长因子-2（FGF-2）与其受体形成复合物，并抑制细胞生长信号。在本研究中，培养牛主动脉内皮细胞，并分析了FGF-2介导的密集和稀疏培养物中syndecan-4表达调节的细胞内信号通路。我们证明了syndecan-4表达的细胞密度依赖性差异调节。具体地说，我们发现FGF-2通过MEK 1/2-ERK 1/2途径在致密细胞培养物中上调血管内皮细胞中syndecan-4的合成，仅在低细胞密度下通过Akt途径转录诱导syndecan-4。这项研究强调了蛋白多糖调节内皮细胞功能的关键机制。
Syndecan-4 is a member of the syndecan family of transmembrane heparan sulfate proteoglycans, and is involved in cell protection, proliferation, and the blood coagulation-fibrinolytic system in vascular endothelial cells. Heparan sulfate chains enable fibroblast growth factor-2 (FGF-2) to form a complex with its receptor and to transduce the cell growth signal. In the present study, bovine aortic endothelial cells were cultured, and the intracellular signal pathways that mediate the regulation of syndecan-4 expression in dense and sparse cultures by FGF-2 were analyzed. We demonstrated the cell density-dependent differential regulation of syndecan-4 expression. Specifically, we found that FGF-2 upregulated the synthesis of syndecan-4 in vascular endothelial cells via the MEK1/2-ERK1/2 pathway in dense cell cultures, with only a transcriptional induction of syndecan-4 at a low cell density via the Akt pathway. This study highlights a critical mechanism underlying the regulation of endothelial cell functions by proteoglycans.