Recombinant hemangiopoietin promotes cell adhesion and binds heparin in its multimeric form

Wang,Li‑Fang; Han,Zhi‑Bo; Li,Mei; Yang,Ping; Xv,Bin; Zhang,Ji‑Ping; Han,Zhong‑Chao

doi:10.3892/mmr.2013.1274

Recombinant hemangiopoietin promotes cell adhesion and binds heparin in its multimeric form

Authors:
- Li‑Fang Wang
- Zhi‑Bo Han
- Mei Li
- Ping Yang
- Bin Xv
- Ji‑Ping Zhang
- Zhong‑Chao Han
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Affiliations: Department of Basic Medicine, Zhejiang Medical College, Hangzhou 310053, P.R. China, State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin 300020, P.R. China, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100010, P.R. China, National Research Center for Stem Cell Engineering and Technology, Tianjin 300020, P.R. China
Published online on: January 15, 2013 https://doi.org/10.3892/mmr.2013.1274
Pages: 959-964

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Abstract

Hemangiopoietin (HAPO) is a novel growth factor stimulating the proliferation of hematopoietic and endothelial progenitor cells in vitro and in vivo. The native protein is a 294‑amino acid multimodular protein. The N‑terminus constitutes of two somatomedin B (SMB) homology domains that contain 14 cysteines. The central region is a putative heparin‑binding domain (pHBD) and the C‑terminus contains mucin‑like repeats. In the present study, we demonstrated that prokaryotic recombinant human HAPO (rhHAPO) self‑associates into a multimeric form with a mass weight of ~129 kDa, suggesting a homologous tetramer. rhHAPO in its multimeric form was found to be more stable and more potent in promoting HESS‑5 cell adhesion. Multimeric rhHAPO had a higher affinity to heparin compared with its dimeric form, although there was no significant conformational change. C‑terminal repeats-truncated rhHAPO (rhHAPOΔmucin) was also found to be assembled into a multimer, while deletion of pHBD (rhHAPOΔmucin‑pHBD) caused the protein to remain in a dimeric form, demonstrating that SMB domains participate in self‑aggregation of the molecule and that the pHBD region promotes the tetramerization.

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