Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Carl-Neuberg-Straße 1, D-30625 Hannover, Germany.
Center for Systems Neuroscience (ZSN), University of veterinary medicine, Bünteweg 2, D-30559 Hannover, Germany.
Int J Mol Sci. 2020 Dec 31;22(1):390. doi: 10.3390/ijms22010390.
Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.
成纤维细胞生长因子 2（FGF-2）在人类和小鼠中广泛表达，在体外和体内功能上参与细胞生长、迁移和成熟。基于相同的 mRNA，人类和啮齿动物翻译出一种 18 千道尔顿（kDa）的 FGF-2 同工型，称为 FGF-2 低分子量（FGF-2LMW）同工型。此外，还存在两种更大的同工型，重量分别为 21 和 22 kDa，总称为 FGF-2 高分子量（FGF-2HMW）同工型。同时，人类 FGF-2HMW 由 22、23、24 和 34 kDa 的蛋白质组成。独立研究证实了 FGF-2 同工型的特定细胞内定位、作用模式和组织特异性时空表达，增加了它们生理和病理生理作用的复杂性。为了分析它们的作用谱，已经生成了 FGF-2LMW 敲除（ko）和 FGF-2HMWko 小鼠，以及特异性过表达 FGF-2LMW 或 FGF-2HMW 的小鼠。到目前为止，已经研究了心血管系统、骨形成和再生的发育和功能，以及它们对中枢神经系统的影响，包括神经退行性疾病模型。这篇综述总结了描述 FGF-2 同工型调节的体内作用的研究，从而全面概述了其在上述器官系统中的作用。
