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Molecules. 2019 Sep 16;24(18). pii: E3360. doi: 10.3390/molecules24183360.

Comparison of the Interactions of Different Growth Factors and Glycosaminoglycans.

Zhang F1, Zheng L2,3, Cheng S4,5, Peng Y6,7, Fu L8, Zhang X9,10, Linhardt RJ11,12,13.

Author information

1
Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. zhangf2@rpi.edu.
2
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. zhenglanhong@126.com.
3
School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China. zhenglanhong@126.com.
4
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. csh_04@163.com.
5
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. csh_04@163.com.
6
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. yanfeipeng@ouc.edu.cn.
7
College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. yanfeipeng@ouc.edu.cn.
8
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. ful3@rpi.edu.
9
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. xingzhang-cas@hotmail.com.
10
School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Wenyuan Road 1, Nanjing 210023, China. xingzhang-cas@hotmail.com.
11
Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. linhar@rpi.edu.
12
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. linhar@rpi.edu.
13
Departments of Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. linhar@rpi.edu.

Abstract

Most growth factors are naturally occurring proteins, which are signaling molecules implicated in cellular multiple functions such as proliferation, migration and differentiation under patho/physiological conditions by interacting with cell surface receptors and other ligands in the extracellular microenvironment. Many of the growth factors are heparin-binding proteins (HBPs) that have a high affinity for cell surface heparan sulfate proteoglycans (HSPG). In the present study, we report the binding kinetics and affinity of heparin interacting with different growth factors, including fibroblast growth factor (FGF) 2,7,10, hepatocyte growth factor (HGF) and transforming growth factor (TGF β-1), using a heparin chip. Surface plasmon resonance studies revealed that all the tested growth factors bind to heparin with high affinity (with KD ranging from ~0.1 to 59 nM) and all the interactions are oligosaccharide size dependent except those involving TGF β-1. These heparin-binding growth factors also interact with other glycosaminoglycans (GAGs), as well as various chemically modified heparins. Other GAGs, including heparan sulfate, chondroitin sulfates A, B, C, D, E and keratan sulfate, showed different inhibition activities for the growth factor-heparin interactions. FGF2, FGF7, FGF10 and HGF bind heparin but the 2-O-sulfo and 6-O-sulfo groups on heparin have less impact on these interactions than do the N-sulfo groups. All the three sulfo groups (N-, 2-O and 6-O) on heparin are important for TGFβ-1-heparin interaction.

KEYWORDS:

glycosaminoglycans; growth factor; heparin; interaction; surface plasmon resonance

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