Jaakkola P, Jalkanen M
Turku Centre for Biotechnology, University of Turku, Finland.
Prog Nucleic Acid Res Mol Biol. 1999;63:109-38. doi: 10.1016/s0079-6603(08)60721-7.
Syndecan-1 is a prototype member of a family of transmembrane heparan sulfate proteoglycans. Syndecan-1 binds extracellular matrix components and fibroblast growth factors (FGFs) and modifies the function of FGFs. Syndecan-1 is constitutively expressed by several epithelial cells, but expression is also induced during many biological phenomena, such as tissue regeneration and the epithelial-mesenchymal interactions during organ development. Growth factors have been the prime candidates to induce syndecan-1 expression in these situations. In fibroblasts syndecan-1 is induced by FGF-2 and in keratinocytes by epidermal growth factor (EGF) and keratinocyte growth factor (KGF). The search for cis-acting elements regulating the growth factor-induced syndecan-1 expression has led to identification of a novel FGF-inducible response element (FiRE). FiRE is activated in fibroblasts and keratinocytes by the same growth factors that induce syndecan-1 expression in these cells. In adult tissues the activation of FiRE is restricted to migrating keratinocytes of healing wounds. The composition of the transcription factor binding to FiRE differs depending on the cell type and the activating growth factor. The FiRE provides a powerful tool for studies on growth factor specificity and regeneration of tissues. Moreover, it implies a novel transcriptional link that creates an FGF action-controlling autoregulatory loop between the heparan sulfate proteoglycans and the heparin-binding FGFs.
Syndecan-1是跨膜硫酸乙酰肝素蛋白聚糖家族的原型成员。Syndecan-1结合细胞外基质成分和成纤维细胞生长因子（FGFs）并改变FGFs的功能。Syndecan-1由多种上皮细胞组成性表达，但在许多生物学现象中也会被诱导表达，如组织再生以及器官发育过程中的上皮-间充质相互作用。在这些情况下，生长因子一直是诱导Syndecan-1表达的主要候选因素。在成纤维细胞中，Syndecan-1由FGF-2诱导，在角质形成细胞中由表皮生长因子（EGF）和角质形成细胞生长因子（KGF）诱导。对调节生长因子诱导的Syndecan-1表达的顺式作用元件的研究，导致了一种新型FGF诱导反应元件（FiRE）的鉴定。FiRE在成纤维细胞和角质形成细胞中被诱导这些细胞中Syndecan-1表达的相同生长因子激活。在成年组织中，FiRE的激活仅限于愈合伤口中迁移的角质形成细胞。与FiRE结合的转录因子的组成因细胞类型和激活生长因子而异。FiRE为研究生长因子特异性和组织再生提供了一个强大的工具。此外，它暗示了一种新的转录联系，在硫酸乙酰肝素蛋白聚糖和肝素结合FGF之间形成了一个控制FGF作用的自动调节环。
