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首页> 外文期刊>Journal of Cellular Physiology >In vitro changes in plasma membrane heparan sulfate proteoglycans and in perlecan expression participate in the regulation of fibroblast growth factor 2 mitogenic activity.
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In vitro changes in plasma membrane heparan sulfate proteoglycans and in perlecan expression participate in the regulation of fibroblast growth factor 2 mitogenic activity.

机译：体外质膜乙酰肝素的变化蛋白聚糖和硫酸perlecan表达式参与调节成纤维细胞生长因子2促有丝分裂的活动。

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摘要

Fibroblast growth factor 1 (FGF1) and 2 (FGF2) bind to two classes of receptors: the high affinity receptors, a family of four known transmembrane tyrosine kinases (FGF R1-R4), and the low affinity receptors, cell surface and basement membrane heparan sulfate proteoglycan (HSPG). During early (first and second) passages of retinal pigmented epithelial (RPE) cells, both FGF1 and FGF2 exhibited low mitogenic activity, while in later (fifth to ninth) passages the activity of FGF1 remained constant but FGF2 activity increased two- to threefold. We have investigated aspects of FGF receptor interactions and the role of heparin/heparan sulfate which modulates FGF activity on RPE cells during in vitro senescence. Northern blot analysis demonstrated that FGF receptor type 1 (FGF R1) is the major high affinity receptor expressed in RPE cells and that its level of expression did not change during serially passage. Both the FGF R1 and the FGF low affinity receptors' binding characteristics (i.e., Kd and number of sites per cell) for FGF1 were unaffected by passage number, whereas the capacity of FGF2 binding to FGF R1 and to the low affinity receptors increased by two- and fivefold, respectively, in late passages, although the affinities were unchanged. This change in the capacity of FGF2 to bind to FGF R1 and to HSPG was not due to a switch of the IIIc splice form of FGF R1 to the IIIb splice form since the exon IIIc was the most predominant splice form of FGF R1 during RPE cell cultures. Furthermore the ratio of the IIIb to the IIIc splice form was not modified during cell subcultures. In parallel in the older RPE cell passages, expression of perlecan, the major FGF low affinity binding site localized on the extracellular matrix of RPE cells, was much elevated compared to early RPE cell passages. Moreover, the cell surface of late passage RPE cells had 79% more HSPG than early passage cells. Therefore, it is suggested that the increase in the number of FGF low affinity receptors present on the cell surface or basement membrane could account for a part of the greater proliferative response of aged RPE cells to FGF2.
机译：纤维母细胞生长因子1 (FGF1)和2 (FGF2)受体的结合两个类:高亲和力受体,一个四口之家跨膜酪氨酸激酶(FGF R1-R4),低亲和力受体,细胞表面基底膜硫酸乙酰肝素蛋白多糖(HSPG)。视网膜色素上皮(RPE)细胞,两者兼而有之FGF1 FGF2表现出低促有丝分裂的活动,而在之后(第五至第九)通道FGF1保持不变,但FGF2的活动活动增加了两到三倍。FGF受体相互作用的研究方面和肝素/硫酸乙酰肝素的作用调节FGF活动在RPE细胞体外衰老。证明FGF受体1型(FGF R1)主要的RPE的高亲和力受体表达细胞和它的表达水平没有在连续通过改变。和FGF低亲和力受体的绑定特征(例如,Kd和网站每个的数量细胞)FGF1被通道数的影响,而FGF2绑定FGF R1的能力和低亲和力受体增加了年末分别两年期和5倍段落,尽管亲和力持平。这种变化在FGF2绑定到的能力FGF R1和HSPG不是由于开关的IIIc接头形式的FGF R1希望拼接形式自外显子IIIc是最主要的接头形式的RPE细胞培养中FGF R1。此外IIIc希望具有的比值接头形式没有修改后的细胞亚文化。主要FGF表达perlecan段落,低亲和力结合位点的本地化RPE细胞的细胞外基质相比早期升高RPE细胞的通道。此外,RPE细胞表面的通道细胞有79%比早期HSPG通道细胞。因此,建议增加FGF低亲和力受体的数量在细胞表面或基底膜占更大的增生性的一部分岁的反应FGF2 RPE细胞。

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