Abstract

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.

Highlights

  • Fibroblast growth factor 2 (FGF-2) belongs to the FGF superfamily comprising at least 22 members in humans (FGF-1-14; FGF-16-23) and rodents (FGF-1-18; FGF-20-23) [1].First isolated from the bovine pituitary gland, it received its primary name due to its pH-dependent dissociation from heparin—basic FGF [2,3,4]

  • We focused on results of studies using both, ko and tg FGF-2 isoform-specific mice, respectively, to provide a thorough characterization of the FGF-2 isoform mediated effects

  • Since the differences in gene expression, protein translation, activation and release of FGF-2 isoforms in the cardiovascular system vary depending on sex, cell type, tissue damage as well as the time point of the analysis, it is a prerequisite to consider each of these factors when examining the FGF-2 mediated effects

Read more

Summary

Introduction

Fibroblast growth factor 2 (FGF-2) belongs to the FGF superfamily comprising at least 22 members in humans (FGF-1-14; FGF-16-23) and rodents (FGF-1-18; FGF-20-23) [1]. The FGF-2HMW isoforms, which display NH2 -terminal extensions of the FGF-2LMW core sequence, have an additional nuclear localization signal restricting their expression predominantly to the cell nucleus and the ribosome [31,32,33,34] This results in an intracrine mode of action by targeting nuclear proteins and transcription factors [35]. Col3.6, collagen 3.6 promoter; FGF-2, fibroblast growth factor 2; H, human; HMW, high molecular weight; kDA, kilo Dalton; ko, knock out; LWW, low molecular weight; PKC, protein kinase C; R, rat; RSV, Rous sarcoma virus long terminal repeat; tg, transgenic

FGF-2 Isoforms in the Cardiovascular System
FGF-2 Isoforms in Bone Physiology
FGF-2 Isoforms in the Central Nervous System
Outlook
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call