Iwabuchi Tokuro, Goetinck Paul F
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Mech Dev. 2006 Nov;123(11):831-41. doi: 10.1016/j.mod.2006.08.003. Epub 2006 Aug 12.
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.
毛发或触须等上皮附属器的发育、维持和再生依赖于体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过程中已被鉴定出的众多信号分子之一。成纤维细胞生长因子（FGFs）等生长因子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（HSPGs），因此这些蛋白聚糖通过形成HSPG、FGFR和FGF的三元信号复合物，作为FGF受体（FGFRs）的共受体。Syndecans构成了一个跨膜HSPGs家族（syndecan-1-4）。在本研究中，我们在器官培养系统中，研究了小鼠触须对HSPG结合生长因子的生长反应与syndecan-4存在与否的关系。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基因敲除小鼠的触须，对FGF-1、FGF-2和FGF-7表现出统计学上显著的剂量依赖性生长反应。相比之下，当培养基中添加与HSPG结合的肝细胞生长因子（HGF）、不与HSPG结合的胰岛素或5%胎牛血清时，野生型和syndecan-4基因敲除小鼠的触须均出现统计学上显著的生长反应。FGF-1、-2和-7对IRS表达基因和参与细胞增殖的基因转录活性的syndecan-4依赖性作用揭示了许多不同的反应模式。在体内，syndecan-4基因敲除小鼠的触须比野生型小鼠的触须更短且直径更小，这种表型可能是由于对生长因子的反应欠佳所致。在触须轴的外根鞘中表达的syndecan-1不影响触须对FGF-1、-2和-7的反应，syndecan-1基因敲除小鼠触须的长度和直径与野生型小鼠的无差异。
