Aigner Achim, Ray Patricio E, Czubayko Frank, Wellstein Anton
Department of Pharmacology and Toxicology, Philipps University, School of Medicine, Karl-von-Frisch-Strasse 1, 35033 Marburg, Germany.
Histochem Cell Biol. 2002 Jan;117(1):1-11. doi: 10.1007/s00418-001-0360-4. Epub 2001 Dec 20.
Fibroblast growth factors (FGFs) play important roles during fetal and embryonic development. FGF-2 (basic FGF, bFGF) is widely expressed in the embryo and has been linked to tissue growth and remodeling. However, it is tightly bound to heparin sulfate proteoglycans of the extracellular matrix which quenches its biological activity. We showed previously that a secreted FGF-binding protein (FGF-BP) can mobilize and activate FGF-2 from the extracellular matrix. While considerable data exist on the expression and pivotal role of FGF-BP in tumor growth, less is known about FGF-BP during embryonic development. In this immunohistochemical study in mice, we show FGF-BP protein expression in a broad spectrum of tissues at various stages between day 8 and day 16 of embryonal development, and compare FGF-BP and FGF-2 immunolocalization. FGF-BP is detected in the digestive system, thymus, skin, hair follicles, dental germ, respiratory tract, various glandular tissues, kidney, liver, and certain areas of the CNS, with immunoreactivity being mainly confined to cells of primitive epithelia. The putative significance of these findings with regard to mobilization of FGF-2 or other molecules is discussed. From the locally confined, time-dependent, and apparently tightly regulated FGF-BP expression we propose that FGF-BP may play an important role in embryonic development.
成纤维细胞生长因子(FGFs)在胎儿和胚胎发育过程中发挥着重要作用。FGF-2(碱性FGF,bFGF)在胚胎中广泛表达,并与组织生长和重塑有关。然而,它与细胞外基质的硫酸乙酰肝素蛋白聚糖紧密结合,从而抑制其生物活性。我们之前表明,一种分泌型FGF结合蛋白(FGF-BP)可以从细胞外基质中动员并激活FGF-2。虽然关于FGF-BP在肿瘤生长中的表达和关键作用已有大量数据,但关于其在胚胎发育过程中的情况却知之甚少。在这项对小鼠的免疫组织化学研究中,我们展示了在胚胎发育第8天至第16天的不同阶段,FGF-BP蛋白在广泛的组织中表达,并比较了FGF-BP和FGF-2的免疫定位。在消化系统、胸腺、皮肤、毛囊、牙胚、呼吸道、各种腺组织、肾脏、肝脏以及中枢神经系统的某些区域检测到FGF-BP,免疫反应性主要局限于原始上皮细胞。讨论了这些发现对于FGF-2或其他分子动员的潜在意义。基于局部受限、时间依赖性且明显受到严格调控的FGF-BP表达,我们提出FGF-BP可能在胚胎发育中发挥重要作用。