Sogos V, Balaci L, Ennas M G, Dell'era P, Presta M, Gremo F
Department of Cytomorphology, School of Medicine, Cagliari, Italy.
Dev Dyn. 1998 Apr;211(4):362-73. doi: 10.1002/(SICI)1097-0177(199804)211:4<362::AID-AJA7>3.0.CO;2-F.
Fibroblast growth factors (FGFs) are believed to play a key role in tissue differentiation and maturation. Thus, the expression of the four members of the high-affinity tyrosine kinase FGF receptor family (FGFRs) and of the low-affinity heparan sulphate proteoglycan binding sites, syndecan-1 and perlecan, was studied in the human skeletal muscle during development. Northern blot analysis demonstrated a developmentally regulated expression of the mRNAs for FGFR-1, FGFR-3, FGFR-4, whereas only traces of FGFR-2 mRNA were found. Each receptor type had a different developmental pattern, suggesting an independent regulation. Signal for FGFR-3 was retained only in the adult muscle. Among the low-affinity FGF binding sites, perlecan was absent, whereas RNA transcript for syndecan-1 peaked at week 13 of gestation, after which a significant decrease was observed. Immunohistochemistry for FGFRs revealed that their localization changed with muscle maturation. At early embryonic stages, FGFR-3 and FGFR-4 had a scattered distribution in the tissue, and FGFR-1 was found on myotube and myofiber plasma membranes. At later stages, FGFR-1 positivity decreased and was found in a few areas of the muscle, FGFR-3 was concentrated in the nuclei of some, but not all, muscle fibers, and FGFR-4 maintained an association with plasma membrane. In adult tissue, weak positivity for FGFR-3 and FGFR-4 was observed in the connective tissue only. When immunocytochemistry was performed on human fetal myoblasts in culture, confocal microscope analysis revealed a nonhomogeneous cell membrane distribution of FGFRs. Taken together, the data strongly suggest that developmentally regulated expression and cell distribution of FGFRs play a role during muscle maturation.
成纤维细胞生长因子（FGFs）被认为在组织分化和成熟过程中起关键作用。因此，我们研究了高亲和力酪氨酸激酶FGF受体家族（FGFRs）的四个成员以及低亲和力硫酸乙酰肝素蛋白聚糖结合位点（syndecan-1和基底膜聚糖）在人类骨骼肌发育过程中的表达情况。Northern印迹分析表明，FGFR-1、FGFR-3、FGFR-4的mRNA表达具有发育调控性，而仅检测到痕量的FGFR-2 mRNA。每种受体类型都有不同的发育模式，提示其表达受独立调控。FGFR-3的信号仅在成年肌肉中保留。在低亲和力FGF结合位点中，未检测到基底膜聚糖，而syndecan-1的RNA转录本在妊娠第13周达到峰值，之后显著下降。FGFRs的免疫组织化学显示，其定位随肌肉成熟而变化。在胚胎早期阶段，FGFR-3和FGFR-4在组织中呈散在分布，FGFR-1则位于肌管和肌纤维的质膜上。在后期阶段，FGFR-1的阳性表达减少，仅在肌肉的少数区域发现，FGFR-3集中在部分（而非全部）肌纤维的细胞核中，FGFR-4则维持与质膜的结合。在成年组织中，仅在结缔组织中观察到FGFR-3和FGFR-4的弱阳性表达。当对培养的人胎儿成肌细胞进行免疫细胞化学检测时，共聚焦显微镜分析显示FGFRs在细胞膜上的分布不均匀。综上所述，这些数据强烈表明，FGFRs的发育调控性表达和细胞分布在肌肉成熟过程中发挥作用。
