Abstract

Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism. The basic FGF and acidic FGF, now known as FGF2 and FGF1, are widely used protein drugs for tissue repair. However, they are susceptible to denaturation at ambient temperatures and during long‐time storage, which will reduce their biological activity. The interaction of FGFs with the sulfated domains of heparan sulfate and heparin is essential for their cellular signaling and stability. Therefore, we analyzed the interactions of FGF1 and FGF2 with four sulfated polysaccharides: heparin, dextran sulfate (DXS), λ‐carrageenan, and chondroitin sulfate. The results of thermal stability and cell proliferation assays demonstrate that heparin, DXS, and λ‐carrageenan bound to both FGFs and protected them from denaturation. Our results suggest heparin, DXS, and λ‐carrageenan are potential formulation materials that bind and stabilize FGFs, and which may also potentiate their activity and control their delivery.

Highlights

  • Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism

  • Since k-carrageenan and dextran sulfate (DXS) are both highly sulfated polysaccharides, their ability to interact with FGF1 was tested

  • The differential scanning fluorimetry (DSF) results indicate that FGF1 binds strongly to both k-carrageenan and DXS, since it is stabilized by both polysaccharides (Fig. 3B,C,E)

Read more

Summary

Introduction

Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism. The basic FGF and acidic FGF, known as FGF2 and FGF1, are widely used protein drugs for tissue repair. They are susceptible to denaturation at ambient temperatures and during long-time storage, which will reduce their biological activity. Activation of the FGFR by the binding of FGF ligand and HS co-receptor induces the activation of the FGFR kinase [3,4,5] This phosphorylates its targets, leading to the activation of many intracellular signaling pathways, for example, RAS-RAF-MAPK and PI3K-AKT, which regulate cell fate and specific cell activities [2,6,7,8].

Objectives
Methods
Results
Conclusion
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