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Journal of Biochemistry Advance Access originally published online on January 29, 2009
Journal of Biochemistry 2009 145(5):653-659; doi:10.1093/jb/mvp021
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© The Authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Induction and Expression of Anti-Angiogenic Vasohibins in the Hematopoietic Stem/Progenitor Cell Population

Hisamichi Naito1, Hiroyasu Kidoya1, Yasufumi Sato2 and Nobuyuki Takakura1,*

1Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan; and 2Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan

*To whom correspondence should be addressed. Tel: +81-6-6879-8316, Fax: +81-6-6879-8314, E-mail: ntakaku{at}biken.osaka-u.ac.jp

Received January 8, 2009; Accepted January 23, 2009


  Abstract

Haematopoiesis and blood vessel formation are closely associated, with several molecules employed by both systems. Recently, vasohibin-1 (VASH1), an endothelium-derived negative feedback regulator of angiogenesis, has been isolated and characterized. VASH1 is induced by VEGF or bFGF in endothelial cells (ECs) and inhibits their proliferation and migration. However, there are no data on the induction and expression of VASH1 in haematopoietic cells (HCs). Here, we show that the haematopoietic stem cell (HSC) population, but not haematopoietic progenitors (HPs) or mature HCs from adult bone marrow (BM) constitutively express VASH1. However, HPs, but not HSCs, can be induced to express VASH1 after BM suppression by 5-FU. Knock-down of the VASH1 gene in VASH1+ leukaemia cells induced cell proliferation. These results suggest a role for VASH1 in negative feedback regulation of HP proliferation during recovery following BM ablation.

Key Words: 5-FU, bone marrow ablation, haematopoietic progenitor cells, haematopoietic stem cell, vasohibin

Abbreviations: bFGF, basic fibroblast growth factor; BM, bone marrow; EC, endothelial cell; HC, haematopoietic cell; HP, haematopoietic progenitor; HSC, haematopoietic stem cell; VASH1, vasohibin-1; VEGF, vascular endothelial growth factor


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