Syndecan-4 dependent FGF stimulation of mouse vibrissae growth.
Syndecan-4 dependent FGF stimulation of mouse vibrissae growth.
复制标题
Syndecan-4 依赖性 FGF 刺激小鼠触毛生长。
DOI：
10.1016/j.mod.2006.08.003
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发表时间：
2006
影响因子：
2.6
通讯作者：
Goetinck,PaulF
中科院分区：
文献类型：
--
作者：
Iwabuchi,Tokuro;Goetinck,PaulF
毛或触须等上皮附属物的发育、维持和再生依赖于珠被的表皮和真皮成分之间的相互作用。生长因子是在这些发育事件中已经确定的许多信号分子之一。生长因子如成纤维细胞生长因子（FGF）在其硫酸乙酰肝素侧链上结合细胞表面硫酸乙酰肝素蛋白聚糖（HSPG），因此这些蛋白聚糖通过形成HSPG、FGFR和FGF的三元信号传导复合物而充当FGF受体（FGFR）的共受体。多配体蛋白聚糖组成跨膜HSPG家族（多配体蛋白聚糖-1-4）。在本研究中，我们研究了在器官培养系统中存在或不存在syndecan-4的小鼠触须对HSPG结合生长因子的生长反应。Syndecan-4在构成触须内根鞘的角质形成细胞上表达。来自野生型小鼠的触须，而不是来自syndecan-4缺失小鼠的触须，显示出对FGF-1、FGF-2和FGF-7的统计学显著的和剂量依赖性的生长反应。相比之下，当培养基补充有结合HSPG的肝细胞生长因子（HGF）、不结合HSPG的胰岛素或5%胎牛血清时，在野生型和syndecan-4缺失小鼠的触须中观察到统计学显著的生长反应。FGF-1、FGF-2和FGF-7对IRS表达基因和参与细胞增殖的基因的转录活性的多配体蛋白聚糖-4依赖性作用揭示了许多不同的反应模式。在体内，多配体蛋白聚糖-4缺失小鼠的触须比野生型小鼠的触须更短并且具有更小的直径，并且这种表型可能是由于对生长因子的次优响应。Syndecan-1，其在触须轴的外根鞘中表达，不影响触须对FGF-1、FGF-2和FGF-7的反应，并且syndecan-1缺失小鼠的触须的长度和直径与野生型小鼠的触须的长度和直径没有差异。
The development, maintenance and regeneration of epithelial appendages such as hairs or vibrissae depend on reciprocal interactions between the epidermal and the dermal components of the integument. Growth factors are among a number of signaling molecules that have been identified during these developmental events. Growth factors such as fibroblast growth factors (FGFs) bind cell surface heparan sulfate proteoglycans (HSPGs) on their heparan sulfate side chains and as such these proteoglycans act as co-receptors for FGF receptors (FGFRs) by forming a ternary signaling complex of HSPG, FGFR and FGF. The syndecans make up a family (syndecan-1–4) of transmembrane HSPGs. In the present study we examined the growth response of mouse vibrissae to HSPG-binding growth factors as a function of the presence or absence of syndecan-4 in an organ culture system. Syndecan-4 is expressed on keratinocytes that make up the inner root sheath of the vibrissa. Vibrissae from wild-type mice, but not from syndecan-4 null mice, displayed a statistically significant and dose-dependent growth response to FGF-1, FGF-2 and FGF-7. In contrast, a statistically significant growth response is seen in vibrissae from both wild-type and syndecan-4 null mice when the culture medium is supplemented with either hepatocyte growth factor (HGF) that binds to HSPG, insulin that does not bind to HSPG or 5% fetal bovine serum. The syndecan-4 dependent effect of FGF-1, -2 and -7 on the transcriptional activity of IRS expressed genes and of genes involved in cell proliferation reveals a number of different response patterns. In vivo, the vibrissae of syndecan-4 null mice are shorter and have a smaller diameter than those of wild-type mice and this phenotype may result from a suboptimal response to growth factors. Syndecan-1, which is expressed in the outer root sheath of the vibrissae shaft, does not influence the response of the vibrissae to FGF-1, -2 and -7 and the length and diameter of vibrissae of syndecan-1 null mice do not differ from those of wild-type mice.